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(Investigative Ophthalmology and Visual Science. 2006;47:3441-3449.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-1035
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A New Locus for Autosomal Dominant Cataract on Chromosome 19: Linkage Analyses and Screening of Candidate Genes

J. Bronwyn Bateman,1,2,3 Leslie Richter,1,3 Pamela Flodman,4 Douglas Burch,1 Sandra Brown,4 Philip Penrose,3,5 Otis Paul,5 David D. Geyer,6,7 David G. Brooks,8,9 and M. Anne Spence4

1From the Department of Ophthalmology, Rocky Mountain Lions Eye Institute, Denver, Colorado; 2The Children’s Hospital, University of Colorado School of Medicine, Denver, Colorado; the 3Eleanor Roosevelt Institute, Denver, Colorado; the 4Department of Pediatrics, University of California, Irvine, California; 5California Presbyterian Medical Center, San Francisco, California; and the 6Scheie Eye Institute and 8Division of Medical Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
PURPOSE. To map and identify the mutated gene for autosomal dominant cataract (ADC) in family ADC4.

METHODS. Ophthalmic evaluations were performed on an American family with ADC and a panel of polymorphic DNA sequence-tagged site (STS) markers for known ADC loci and other genome-wide polymorphic markers were used to map the gene; two-point lod scores were calculated. Fine mapping was undertaken in the chromosomal regions of maximum lod scores, and candidate genes were sequenced.

RESULTS. A four-generation American family with ADC was studied. The only phakic individual exhibited white and vacuolated opacities in the cortical region. This ADC locus mapped to several suggestive chromosomal regions. Assuming full penetrance, the highest calculated maximum lod score was 3.91 with D19S902. On chromosome 12, we sequenced all exons and the exon–intron borders of the membrane intrinsic protein (MIP) gene. On chromosome 19, all exons and the exon–intron borders of genes for lens intrinsic membrane2 (LIM2), ferritin light chain (FTL), and the human homologue of the Drosophila sine oculis homeobox 5 (SIX5) were sequenced, and the 3' untranslated repeat region (UTR) of the dystrophy (DMPK) gene and both the 5' and 3' UTRs of the SIX5 genes were amplified; the promoter for LIM2 was sequenced. For these genes, the sequence matched that in the reference libraries, and the DMPK gene had a normal number of CTG repeats.

CONCLUSIONS. The mutated gene in ADC4 probably represents a new, not yet identified locus on chromosome 19. In one phakic member, the cortical cataracts were punctate and vacuolated.

Pediatric cataracts are an important and treatable cause of visual impairment in infancy. Because of different definitions of visual impairment and blindness, regional socioeconomic standards and healthcare systems, and study methodology including ascertainment, estimates of the prevalence of blindness and infantile cataract in the United States and worldwide vary. The economic and personal impact of pediatric cataracts is unknown but significant in all cultures, because the predicted number of blind years is greater in children than adults. In developed countries, the prevalence rate varies from 0.63 to 13.6 per 10,000 births1 2 3 4 or infants under the age of 1 year.5 6 In the United States, SanGiovanni et al.6 estimated the prevalence of infantile cataracts to be 13.6 per 10,000 infants under the age of 1 year, based on a database collected prospectively from the late 1960s and early 1970s. Spanning the years 1968 to 1998, Bhatti et al.3 calculated a U.S. rate of 2.03 infants with cataracts per 10,000 births, based on retrospective analyses.

The causes of pediatric cataracts are diverse and include infectious agents and genetic defects. For the autosomal dominant form (ADC), neither the incidence nor the prevalence is known. ADC forms are usually bilateral. In developed countries, bilateral isolated cataracts account for between 44% and 66% of infantile cataracts3 7 ; unilateral, isolated cataracts comprise between 25% and 60%.3 7 Nearly 90% of bilateral, hereditary cataracts were autosomal dominant, based on a large British study.7 In Denmark, 46% of bilateral, isolated cataracts were determined to be genetic.8

ADC is a clinically and genetically heterogeneous disease. ADCs have been classified clinically on the bases of the morphology, size, color, and location of the opacities in the lens or the name of the investigator describing the cataract or affected family. Although ophthalmologists have developed cataract nomenclature, Francis et al.9 devised a system for conformity. Wide variations of cataract types among families have been documented including nuclear,10 anterior polar,11 posterior polar,12 coralliform,13 blue dot cerulean,14 pulverulent,15 cortical,16 zonular,17 and sutural cataracts.18 The same phenotype may be caused by mutations of different genes and the identical gene mutation has been reported to cause diverse cataracts in different families. For example, posterior polar cataracts may be caused by mutations of paired-like homeodomain transcription factor 3,19 a transcription factor on chromosome 10 or the crystallin protein crystallin alpha B20 on chromosome 11. Conversely, a mutation of the crystallin, beta B2 (475C->T) has been associated with sutural cataract21 in one family, cerulean cataract22 in another, and a Coppock-like cataract23 in a third; morphology was consistent within each family. Despite attempts to categorize hereditary cataracts clinically, there is limited correlation of phenotypes with genetic locus and specific mutation.

ADCs exhibit high penetrance, and many genetic loci have been identified by linkage and mutational analyses. Twenty-four chromosomal regions have been implicated for ADC, and 15 ADC genes have been identified in these regions, including those encoding for membrane proteins connexins (gap junction, alpha 824 25 and gap junction, alpha 326 27 28 29 ), membrane junction proteins (major intrinsic protein of lens fiber30 ), crystallins (gamma C,31 gamma D,31 32 33 34 35 36 37 beta A1,28 35 38 39 40 41 beta B2,21 22 23 42 beta B1,43 alpha B,20 and alpha A [Xi JH, et al. IOVS 2002;43:ARVO E-Abstract 3556],44 45 ), structural proteins (beaded filament structural protein 2),46 47 48 intracellular storage proteins (ferritin light chain),49 50 51 52 53 54 55 56 57 58 transcription factors (paired-like homeodomain transcription factor 3,19 59 60 paired box gene 6,61 62 and v-mafmusculoaponeurotic fibrosarcoma oncogene homolog (avian)63 ), and heat shock proteins (heat shock transcription factor 4).64 With few exceptions, the mutations are personal, not supporting a founder effect.

We studied a four-generation family with some members affected with ADC. Ophthalmic evaluations and linkage analyses using genome-wide polymorphic DNA markers were performed, and two-point lod scores were calculated. We undertook fine mapping in the regions of suggestive and statistically significant maximum lod scores and performed multipoint analyses. We screened or sequenced candidate genes.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Patients and Clinical Findings
The study adhered to the tenets of the Declaration of Helsinki for research involving human subjects. Informed consent was obtained before examination. A four-generation American family of white ancestry (ADC4; Fig. 1 ) was studied. Individuals 6 and 15 were used for some sequencing studies but not for the linkage analyses. During the study, some new individuals were identified, and one key unaffected individual died. All linkage analyses were performed with sufficient power.


Figure 1
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  		FIGURE 1. Pedigree of ADC4 family with haplotypes in the mapped region of chromosome 19. The pedigree has been modified slightly, to protect the confidentiality of the family. Affected individuals are annotated as solid symbols; numbers indicate individuals studied (examined, samples obtained). Haplotypes in the critical region on chromosome 19 are indicated below each individual studied for linkage in this region, and the conserved region is in a shaded box. *Individuals from whom DNA was collected.

 
Individuals were examined by slit lamp biomicroscopy or retroillumination (in the field) after pupillary dilation. Affected status was determined by observed opacities or history of cataract extraction before the age of 50 years. The pedigree showed a vertical pattern of inheritance including male-to-male transmission; both genders were similarly affected.

Linkage Analyses
Blood samples were collected in acid citrate dextrose (ACD; BD Vacutainer, Franklin Lakes, NJ), and DNA was extracted. We analyzed polymorphic sequence-tagged site (STS) DNA markers using our 1998 ADC Screening Panel and previously described methodology (Table 1) .39 As the original 1998 Panel had expanded after reports of ADC gene mutations, markers were added and some were analyzed in this family. We used linkage mapping (Prism Linkage Mapping Set, ver. 2.0 and 2.5; Applied Biosystems, Inc. [ABI], Foster City, CA); we performed a genome-wide screening; and we analyzed panels of fluorescent primers for polymorphic STS markers, on average 10 cM apart, as detailed in the user’s manual. The PCR genotypes were analyzed on computer (GeneScan and GeneMapper, ver. 3.5.1 software; ABI).


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  		TABLE 1. ADC Panel Markers and Lod Scores with ADC4 Locus

 
Two point lod scores were calculated using the LIPED algorithm (http://linkage.rockefeller.edu/ provided in the public domain by Rockefeller University, New York, NY).65 A gene frequency of 0.0001 and full penetrance were assumed for the cataract locus. Two-point lod scores were calculated for a full range of {theta}m and {theta}f values. Accurate population-specific allele frequency data are not available for these markers. Therefore, in the regions of interest, we used a range of possible allele frequencies to assess the robustness of the allele frequency assumptions. For these data, the effect on the results was negligible.

The genome-wide coverage was checked by using both the recombination and physical map locations for each marker. We classified lod scores as suggestive or statistically significant. We assessed regions with suggestive lod scores with additional markers and multipoint analyses, and sequenced good candidate genes in the area. We accepted lod scores greater than 3.0 as statistically significant and indicative of significant evidence for linkage with the marker; for statistically significant lod scores, we sequenced all good candidate genes in the region.

Multipoint linkage analyses were undertaken using the FASTLINK66 implementation of the MLINK and LINKMAP programs (http:www.hgmp.mrc.ac.uk/; provided in the public domain by the Human Genome Mapping Project Resources Centre, Cambridge, UK),67 68 and Genehunter 2.1 (Rockefeller University).69 For the Genehunter analyses, it was possible to calculate exact multipoint lod scores using the full pedigree and all 14 markers from chromosome 19, by increasing the "max bits" parameter to 24.

Screening for Candidate Genes
Identification of candidate genes was based on previous reports of mutations of genes causing ADC or on expression and function, using the National Center for Biotechnology Information’s Mapviewer.70

We sequenced candidate genes in regions suggestive of linkage on chromosomes 12 and 19 including all exons and exon–intron borders of MIP on chromosome 12 as well as the lens intrinsic membrane2 (LIM2), the homologue of the Drosophila sine oculis homeobox 5 gene (SIX5), and FTL genes on chromosome 19. The 3' untranslated region of the dystrophia myotonica protein kinase gene (DMPK) on chromosome 19 was sized for CTG repeats. In addition, the LIM2 promoter region and the 5' and 3' untranslated regions (UTRs) of the SIX5 gene were sequenced. Primers were designed for the LIM2, MIP, and SIX5 candidate genes based on reference sequences from NCBI70 and/or Ensembl71 (Table 2) . Previously described primers and conditions were used to amplify the repeat region in the DMPK gene (UniSTS:34269) and the exons and intron–exon borders of the FTL gene.72 A minor modification was applied to the FTL PCR; the 5' UTR and exon 1 were amplified in the same reaction using the forward primer 5'-TCCTTGCCACCGCAGATTG-3' and the reverse primer 5'-GCAGCTGGAGGAAATTA-3'. For LIM2, PCR products were sequenced from both directions using a dye terminator cycle sequencing kit (Prism FS; ABI) and an automated fluorescence sequencer (model 373; ABI). For DMPK, the 3' repeat region was amplified (UniSTS:34269) and PCR products were resolved on 2% SFR agarose (Midwest Scientific, St. Louis, MO) gels. For SIX5 and MIP, PCR products were amplified (Taq PCR Core kit; Qiagen, Valencia, CA). PCR reactions were run with 25 ng of genomic DNA, 1.5 mM MgCl2, 0.5 mM dNTP, 0.4 µM each primer, and 0.5 units Taq polymerase. We sequenced PCR products using dye termination chemistry and a genetic analyzer (Big Dye ver. 3.0 or ver. 1.1 terminator kits and both a 3100 Genetic Analyzer and a 3100-Avant Genetic Analyzer; all ABI). Sequence analyses were performed using Consed.73 Two unaffected and two affected family members were sequenced for the MIP (members 6, 11, 12, and 15) and FTL (members 11, 16, 21, and 22) genes. All family members were sequenced for LIM2 and SIX5, and sized for the DMPK repeat region. Ferritin level was measured in one affected individual (11) in a commercial laboratory.


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  		TABLE 2. Primers for LIM2, SIX5, and MIP

 

   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Patients and Clinical Findings
Based on office slit lamp biomicroscopy of the only known phakic individual (16), the ADC4 cataracts were irregularly shaped white or spherically shaped vacuolated opacities symmetrically located in the cortical region of lens (Fig. 2) . Phenotypic variability is unknown.


Figure 2
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  		FIGURE 2. Right lens of proband. Left: white flecks were evident in the cortical region of the lens (direct illumination). Center: vacuoles were visible in the cortical region. Right: magnification of vacuoles and white opacities in the cortex. (Courtesy Denice Barsness, CRA, COMT, ROUB, FOPS, California Pacific Medical Center, San Francisco, CA.)

 
Linkage Analyses
Both the focused and genome-wide screen employing 268 markers was completed on the family. We excluded linkage to regions of known ADC loci (Table 1) except for chromosome 12 (maximum lod score of 2.71 with D12S102 for {theta}f = {theta}m =0); multipoint analysis did not further support a locus in this suggestive region. For the genome-wide screening, a plausible indication of linkage, based on two-point linkage analysis, was found on chromosome 17 (maximum lod score of 1.55 with D17S1806 for {theta}m = 0.403 and {theta}f = 0.00); multipoint analyses in this region failed to confirm evidence of linkage. All other chromosomal regions were either excluded by the lod score or by multipoint analysis except for areas on chromosome 19. The maximum lod score was on chromosome 19 (3.91 for D19S903, {theta}f = {theta}m = 0; Table 3 ). Therefore, the only remaining region of the genome with evidence for linkage of the cataract and genetic markers is chromosome 19 (data available from the authors by request). Visual inspection of haplotypes (Fig. 1) and multipoint analysis (Fig. 3) indicated that the most likely chromosomal region lies between markers D19S220 and D19S902.


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  		TABLE 3. Lod Scores between ADC4 Disease Locus and Polymorphic Markers on Chromosome 19

 

Figure 3
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  		FIGURE 3. Multipoint analysis of mapped regions of chromosome 19.

 
Screening of Candidate Genes
MIP on the long arm of chromosome 12 was the candidate gene on our ADC panel and the marker D12S102 is 10.07 Mb distal to this candidate gene. On the long arm of chromosome 19, we identified four candidate genes (LIM2, FTL, DMPK, and SIX5) within 6.83 Mb distal to 19S902.

For the exons and intron–exon borders sequenced for MIP, LIM2, SIX5, and FTL, our sequence was the same in all individuals tested and matched that in the reference libraries. The LIM2 promoter and the SIX5 5' and 3' UTRs matched reference sequences. The number of repeat CTG sequence for DMPK in ranged from four to nine, below the 50 repeats or greater found in individuals affected with myotonic dystrophy. The ferritin level was 30 ng/mL in affected individual 11, within the reference range of 10 to 291 ng/mL.


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
The clinical features of the cataract in this family are not unique based on the office examination of the one affected phakic member. The prominent vacuoles are suggestive of a water and/or ion transport defect.

We sequenced the MIP gene on chromosome 12 that was in the region suggestive of linkage. MIP is the predominant membrane protein74 75 in the lens. The homologous region of human chromosome 12, region q13, is mouse chromosome 10. Mutations of Mip (MP26) cause cataracts in the Fraser (CatFr),76 77 lens opacity mutations (Lop),77 hydropic fiber (Hfi),78 and Tohoku79 mice. In humans, missense mutations in exon 2 of MIP on the long arm of chromosome 12 (12q13) have been the basis of ADC in previously reported families.30 80

We identified the most likely region for the ADC gene in this family on chromosome 19 based on a lod score of 3.91 with D19S903. Fine mapping narrowed the region of the putative gene to a 10-cM (10-Mb) region on chromosome 19 flanked by D19S220 and D19S902. The long arm of chromosome 19 has several interesting candidate genes that are expressed in the lens and are known to cause cataracts in mice and/or humans. We sequenced the exons and the intron–exon borders of the gene encoding MIP on chromosome 12 and genes for LIM2, SIX5, and FTL on chromosome 19 in members of this family; the exons and the intron–exon borders matched the reference sequence in all. The number of CTG repeats in the 3' untranslated DM1 region of DMPK on chromosome 19 was normal.

LIM2, an ideal candidate as the protein MP-20 (formerly MP-19) is expressed in the lens,81 is 20 kDa and has four domains within the membrane.82 Mutations of the gene in the To3 mouse cause a semidominant congenital cataract83 84 85 ; transgenic mice have cataracts.86 Although the function of the protein is uncertain, it may play a role in the cellular transition from proliferation.87 Zhou et al.88 found similar proteins from primitive species such as Chlamydia and suggested important functions such as transport or enzymatic activities. In mouse studies, this protein regulates fiber cell differentiation.89 Mutations of LIM2 have been reported to cause an autosomal recessive presenile cataract in one family.90

Cataracts may occur as early as the teenage years in individuals with myotonic dystrophy. Myotonic dystrophy (DM1) is caused by an unstable repeat DNA sequence of triplet nucleotides (CTG) in the 3' noncoding region of the myotonic dystrophy gene (DMPK) that encodes a serine-threonine protein kinase. An increased number of CTG repeats cause the disease. A second myotonic dystrophy locus is on chromosome 3. It is likely that there are several mechanisms for the disease. Altered splicing of the DMPK transcript may cause retention of the transcript in the nucleus,91 92 93 94 or the DMPK RNA CUG repeat may exert a toxic gain-of-function on cellular metabolism.95 Of importance in cataract formation, the expanded CTG nucleotide repeat may alter expression of neighboring genes. The expansion alters local chromatin structure and suppresses the expression of the SIX5 gene,96 97 98 which is the gene after the 3' end of the DMPK gene. As cataracts develop in mice with one or two defective copies of the SIX5 gene,99 100 altered expression of the SIX5 gene may be the basis of cataracts in myotonic dystrophy. SIX5 transcripts are expressed in the adult epithelium of the cornea, lens, and ciliary body as well as the retina and sclera but are not expressed in the fetal eye.101 We postulated that either an unusual clinical manifestation of myotonic dystrophy (cataracts alone) or a mutation of the SIX5 gene may be the basis for the ADC4 phenotype. However, the sequence of SIX5 gene and the number of repeats in the 3' noncoding region of the DMPK gene in key members of this family were normal.

Hyperferritinemia is an ADC disorder with elevated serum levels of the light chain of ferritin.102 Patients are asymptomatic aside from cataracts; however, there are mild abnormalities on liver biopsy. Many mutations of the light-chain ferritin gene have been reported from diverse regions of the world.49 50 51 52 53 54 55 56 57 58 72 103 104 105 106 107 We found normal ferritin DNA sequence in two affected individuals and a normal ferritin level in one.

An autosomal recessive congenital nuclear cataract locus has been mapped recently to the 19q13 region in a large consanguineous Pakistani family108 ; in this family, the most likely region for the gene is between D19S928 and D19S425, based on homozygosity of the region in four affected siblings. The locus in our family probably maps to a more distal region. As Riazuddin et al.108 note, the distal obligate crossover event in their family is with marker D19S420. If this marker is taken as the distal flanking marker in their family, there is a small region of overlap with the mapped region between D19S213 and D19S420 (10 Mb) in our family. Although the lod scores in this area of overlap cannot completely exclude the region as containing a causative gene in both families, the most likely interpretation is that a different gene is involved in each family.

Based on linkage analyses and sequencing data, our ADC4 family with one member affected with irregularly shaped white or spherically shaped vacuolated cortical opacities probably represents a new locus on the short arm of chromosome 19.


   Acknowledgements
 
The authors thank Linda Nguyen for assistance with processing the data.


   Footnotes
 
7 Deceased January 10, 2006. Back

9 Present affiliation: Merck & Co, Whitehouse Station, New Jersey. Back

Supported by National Eye Institute Grant EY08282 (JBB).

Submitted for publication August 5, 2005; revised October 6, 2005, and March 31, 2006; accepted June 19, 2006.

Disclosure: J.B. Bateman, None; L. Richter, None; P. Flodman, None; D. Burch, None; S. Brown, None; P. Penrose, None; O. Paul, None; D.D. Geyer, None; D.G. Brooks, None; M.A. Spence, None

The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Corresponding author: J. Bronwyn Bateman, Department of Ophthalmology, University of Colorado, 1675 N. Ursula Street, Box F-731, Aurora, CO 80045; bronwyn.bateman{at}uchsc.edu.


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Stoll C, Alembik Y, Dott B, Roth MP. Epidemiology of congenital eye malformations in 131,760 consecutive births. Ophthalmic Paediatr Genet. 1992;13:179–186.[ISI][Medline][Order article via Infotrieve]
  2. Bermejo E, Martinez-Frias ML. Congenital eye malformations: clinical-epidemiological analysis of 1,124,654 consecutive births in Spain. Am J Med Genet. 1998;75:497–504.[CrossRef][ISI][Medline][Order article via Infotrieve]
  3. Bhatti TR, Dott M, Yoon PW, Moore CA, Gambrell D, Rasmussen SA. Descriptive epidemiology of infantile cataracts in metropolitan Atlanta, GA, 1968–1998. Arch Pediatr Adolesc Med. 2003;157:341–347.[Abstract/Free Full Text]
  4. Wirth MG, Russell-Eggitt IM, Craig JE, Elder JE, Mackey DA. Aetiology of congenital and paediatric cataract in an Australian population. Br J Ophthalmol. 2002;86:782–786.[Abstract/Free Full Text]
  5. Rahi JS, Dezateaux C. Measuring and interpreting the incidence of congenital ocular anomalies: lessons from a national study of congenital cataract in the UK. Invest Ophthalmol Vis Sci. 2001;42:1444–1448.[Abstract/Free Full Text]
  6. SanGiovanni JP, Chew EY, Reed GF, et al. Infantile cataract in the collaborative perinatal project: prevalence and risk factors. Arch Ophthalmol. 2002;120:1559–1565.[Abstract/Free Full Text]
  7. Rahi JS, Dezateux C. Congenital and infantile cataract in the United Kingdom: underlying or associated factors. British Congenital Cataract Interest Group. Invest Ophthalmol Vis Sci. 2000;41:2108–2114.[Abstract/Free Full Text]
  8. Haargaard B, Wohlfahrt J, Fledelius HC, Rosenberg T, Melbye M. A nationwide Danish study of 1027 cases of congenital/infantile cataracts: etiological and clinical classifications. Ophthalmology. 2004;111:2292–2298.[CrossRef][ISI][Medline][Order article via Infotrieve]
  9. Francis PJ, Berry V, Bhattacharya SS, Moore AT. The genetics of childhood cataract. J Med Genet. 2000;37:481–488.[Abstract/Free Full Text]
  10. Lee JB, Benedict WL. Hereditary nuclear cataract. AMA Arch Ophthalmol. 1950;44:643–650.[ISI][Medline][Order article via Infotrieve]
  11. Jaafar MS, Robb RM. Congenital anterior polar cataract: a review of 63 cases. Ophthalmology. 1984;91:249–254.[ISI][Medline][Order article via Infotrieve]
  12. Tulloh CG. Hereditary posterior polar cataract with report of a pedigree. Br J Ophthalmol. 1955;39:374–379.[Free Full Text]
  13. Gunn RM. Peculiar coralliform cataract with crystals in the lens. Trans Ophthalmol Soc UK. 1895;15:119.
  14. Armitage MM, Kivlin JD, Ferrell RE. A progressive early onset cataract gene maps to human chromosome 17q24. Nat Genet. 1995;9:37–40.[CrossRef][ISI][Medline][Order article via Infotrieve]
  15. Mackay D, Ionides A, Berry V, Moore A, Bhattacharya S, Shiels A. A new locus for dominant "zonular pulverulent" cataract, on chromosome 13. Am J Hum Genet. 1997;60:1474–1478.[ISI][Medline][Order article via Infotrieve]
  16. Ionides A, Francis P, Berry V, et al. Clinical and genetic heterogeneity in autosomal dominant cataract. Br J Ophthalmol. 1999;83:802–808.[Abstract/Free Full Text]
  17. Basti S, Hejtmancik JF, Padma T, et al. Autosomal dominant zonular cataract with sutural opacities in a four-generation family. Am J Ophthalmol. 1996;121:162–168.[ISI][Medline][Order article via Infotrieve]
  18. Vanita Singh JR, Sarhadi VK, et al. A novel form of "central pouchlike" cataract, with sutural opacities, maps to chromosome 15q21–22. Am J Hum Genet. 2001;68:509–514.[CrossRef][ISI][Medline][Order article via Infotrieve]
  19. Finzi S, Li YY, Mitchell TN, Farr A, Sundin O, Maumenee IH. Posterior polar cataract: clinical spectrum and genetic analysis in a large family (Abstract). American Society of Human Genetics (ASHG); Annual Meeting. 2002;1656.
  20. Berry V, Francis P, Reddy MA, et al. Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. Am J Hum Genet. 2001;69:1141–1145.[CrossRef][ISI][Medline][Order article via Infotrieve]
  21. Vanita Sarhadi V, Reis A, et al. A unique form of autosomal dominant cataract explained by gene conversion between beta-crystallin B2 and its pseudogene. J Med Genet. 2001;38:392–396.[Free Full Text]
  22. Litt M, Carrero-Valenzuela R, LaMorticella DM, et al. Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta-crystallin gene CRYBB2. Hum Mol Genet. 1997;6:665–668.[Abstract/Free Full Text]
  23. Gill D, Klose R, Munier FL, et al. Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2. Invest Ophthalmol Vis Sci. 2000;41:159–165.[Abstract/Free Full Text]
  24. Shiels A, Mackay D, Ionides A, Berry V, Moore A, Bhattacharya S. A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q. Am J Hum Genet. 1998;62:526–532.[CrossRef][ISI][Medline][Order article via Infotrieve]
  25. Willoughby CE, Arab S, Gandhi R, et al. A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract. J Med Genet. 2003;40:E124.[Medline][Order article via Infotrieve]
  26. Mackay D, Ionides A, Kibar Z, et al. Connexin46 mutations in autosomal dominant congenital cataract. Am J Hum Genet. 1999;64:1357–1364.[CrossRef][ISI][Medline][Order article via Infotrieve]
  27. Jiang H, Jin Y, Bu L, et al. A novel mutation in GJA3 (connexin46) for autosomal dominant congenital nuclear pulverulent cataract. Mol Vis. 2003;9:579–583.[ISI][Medline][Order article via Infotrieve]
  28. Qi Y, Jia H, Huang S, et al. A deletion mutation in the betaA1/A3 crystallin gene (CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family. Hum Genet. 2004;114:192–197.[CrossRef][ISI][Medline][Order article via Infotrieve]
  29. Bennett TM, Mackay DS, Knopf HL, Shiels A. A novel missense mutation in the gene for gap-junction protein alpha3 (GJA3) associated with autosomal dominant "nuclear punctate" cataracts linked to chromosome 13q. Mol Vis. 2004;10:376–382.[ISI][Medline][Order article via Infotrieve]
  30. Berry V, Francis P, Kaushal S, Moore A, Bhattacharya S. Missense mutations in MIP underlie autosomal dominant ‘polymorphic’ and lamellar cataracts linked to 12q. Nat Genet. 2000;25:15–17.[CrossRef][ISI][Medline][Order article via Infotrieve]
  31. Heon E, Priston M, Schorderet DF, et al. The gamma-crystallins and human cataracts: a puzzle made clearer. Am J Hum Genet. 1999;65:1261–1267.[CrossRef][ISI][Medline][Order article via Infotrieve]
  32. Stephan DA, Gillanders E, Vanderveen D, et al. Progressive juvenile-onset punctate cataracts caused by mutation of the gammaD-crystallin gene. Proc Natl Acad Sci USA. 1999;96:1008–1012.[Abstract/Free Full Text]
  33. Nandrot E, Slingsby C, Basak A, et al. Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts. J Med Genet. 2003;40:262–267.[Abstract/Free Full Text]
  34. Mackay DS, Andley UP, Shiels A. A missense mutation in the gammaD crystallin gene (CRYGD) associated with autosomal dominant "coral-like" cataract linked to chromosome 2q. Mol Vis. 2004;10:155–162.[ISI][Medline][Order article via Infotrieve]
  35. Burdon KP, Wirth MG, Mackey DA, et al. Investigation of crystallin genes in familial cataract, and report of two disease associated mutations. Br J Ophthalmol. 2004;88:79–83.[Abstract/Free Full Text]
  36. Xu WZ, Zheng S, Xu SJ, Huang W, Yao K, Zhang SZ. Autosomal dominant coralliform cataract related to a missense mutation of the gammaD-crystallin gene. Chin Med J (Engl). 2004;117:727–732.[Medline][Order article via Infotrieve]
  37. Shentu X, Yao K, Xu W, Zheng S, Hu S, Gong X. Special fasciculiform cataract caused by a mutation in the gammaD-crystallin gene. Mol Vis. 2004;10:233–239.[ISI][Medline][Order article via Infotrieve]
  38. Kannabiran C, Rogan PK, Olmos L, et al. Autosomal dominant zonular cataract with sutural opacities is associated with a splice mutation in the betaA3/A1-crystallin gene. Mol Vis. 1998;4:21.[Medline][Order article via Infotrieve]
  39. Bateman JB, Geyer DD, Flodman P, et al. A new betaA1-crystallin splice junction mutation in autosomal dominant cataract. Invest Ophthalmol Vis Sci. 2000;41:3278–3285.[Abstract/Free Full Text]
  40. Qi YH, Jia HY, Huang SZ, et al. [Autosomal dominant congenital nuclear cataract caused by a deletion mutation in the beta A1-crystallin gene]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003;20:486–489.[Medline][Order article via Infotrieve]
  41. Ferrini W, Schorderet DF, Othenin-Girard P, Uffer S, Heon E, Munier FL. CRYBA3/A1 gene mutation associated with suture-sparing autosomal dominant congenital nuclear cataract: a novel phenotype. Invest Ophthalmol Vis Sci. 2004;45:1436–1441.[Abstract/Free Full Text]
  42. Santhiya ST, Manisastry SM, Rawlley D, et al. Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene. Invest Ophthalmol Vis Sci. 2004;45:3599–3607.[Abstract/Free Full Text]
  43. Mackay DS, Boskovska OB, Knopf HL, Lampi KJ, Shiels A. A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q. Am J Hum Genet. 2002;71:1216–1221.[CrossRef][ISI][Medline][Order article via Infotrieve]
  44. Litt M, Kramer P, LaMorticella DM, Murphey W, Lovrien EW, Weleber RG. Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Hum Mol Genet. 1998;7:471–474.[Abstract/Free Full Text]
  45. Mackay DS, Andley UP, Shiels A. Cell death triggered by a novel mutation in the alphaA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q. Eur J Hum Genet. 2003;11:784–793.[CrossRef][ISI][Medline][Order article via Infotrieve]
  46. Jakobs PM, Hess JF, FitzGerald PG, Kramer P, Weleber RG, Litt M. Autosomal-dominant congenital cataract associated with a deletion mutation in the human beaded filament protein gene BFSP2. Am J Hum Genet. 2000;66:1432–1436.[CrossRef][ISI][Medline][Order article via Infotrieve]
  47. Conley YP, Erturk D, Keverline A, et al. A juvenile-onset, progressive cataract locus on chromosome 3q21–q22 is associated with a missense mutation in the beaded filament structural protein-2. Am J Hum Genet. 2000;66:1426–1431.[CrossRef][ISI][Medline][Order article via Infotrieve]
  48. Zhang Q, Guo X, Xiao X, Yi J, Jia X, Hejtmancik JF. Clinical description and genome wide linkage study of Y-sutural cataract and myopia in a Chinese family. Mol Vis. 2004;10:890–900.[ISI][Medline][Order article via Infotrieve]
  49. Beaumont C, Leneuve P, Devaux I, et al. Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. Nat Genet. 1995;11:444–446.[CrossRef][ISI][Medline][Order article via Infotrieve]
  50. Girelli D, Olivieri O, De Franceschi L, Corrocher R, Bergamaschi G, Cazzola M. A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract. Br J Haematol. 1995;90:931–934.[ISI][Medline][Order article via Infotrieve]
  51. Aguilar-Martinez P, Biron C, Masmejean C, Jeanjean P, Schved JF. A novel mutation in the iron responsive element of ferritin L-subunit gene as a cause for hereditary hyperferritinemia-cataract syndrome (Letter; comment). Blood. 1996;88:1895.[Free Full Text]
  52. Cazzola M, Bergamaschi G, Tonon L, et al. Hereditary hyperferritinemia-cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA (see comments). Blood. 1997;90:814–821.[Abstract/Free Full Text]
  53. Girelli D, Corrocher R, Bisceglia L, et al. Hereditary hyperferritinemia-cataract syndrome caused by a 29-base pair deletion in the iron responsive element of ferritin L-subunit gene. Blood. 1997;90:2084–2088.[Abstract/Free Full Text]
  54. Martin ME, Fargion S, Brissot P, Pellat B, Beaumont C. A point mutation in the bulge of the iron-responsive element of the L ferritin gene in two families with the hereditary hyperferritinemia–cataract syndrome (see comments). Blood. 1998;91:319–323.[Abstract/Free Full Text]
  55. Mumford AD, Vulliamy T, Lindsay J, Watson A. Hereditary hyperferritinemia-cataract syndrome: two novel mutations in the L-ferritin iron-responsive element (Letter; comment). Blood. 1998;91:367–368.[Free Full Text]
  56. McLeod JL, Craig J, Gumley S, Roberts S, Kirkland MA. Mutation spectrum in Australian pedigrees with hereditary hyperferritinaemia-cataract syndrome reveals novel and de novo mutations. Br J Haematol. 2002;118:1179–1182.[CrossRef][ISI][Medline][Order article via Infotrieve]
  57. Garderet L, Hermelin B, Gorin NC, Rosmorduc O. Hereditary hyperferritinemia-cataract syndrome: a novel mutation in the iron-responsive element of the L-ferritin gene in a French family. Am J Med. 2004;117:138–139.[ISI][Medline][Order article via Infotrieve]
  58. Simsek S, Nanayakkara PW, Keek JM, Faber LM, Bruin KF, Pals G. Two Dutch families with hereditary hyperferritinaemia-cataract syndrome and heterozygosity for an HFE-related haemochromatosis gene mutation. Neth J Med. 2003;61:291–295.[ISI][Medline][Order article via Infotrieve]
  59. Semina EV, Ferrell RE, Mintz-Hittner HA, et al. A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Nat Genet. 1998;19:167–170.[CrossRef][ISI][Medline][Order article via Infotrieve]
  60. Yang Z, Pellerano G, Valdez-Guerrero ME, et al. A novel mutation in PITX3 associated with an autosomal dominant form of congenital cataract (Abstract). ASHG Annual Meeting. 2002.2080.
  61. Glaser T, Jepeal L, Edwards JG, Young SR, Favor J, Maas RL. PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects (published correction appears in Nat Genet. 1994;8:203). Nat Genet. 1994;7:463–471.[CrossRef][ISI][Medline][Order article via Infotrieve]
  62. Azuma N, Yamaguchi Y, Handa H, Hayakawa M, Kanai A, Yamada M. Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies. Am J Hum Genet. 1999;65:656–663.[CrossRef][ISI][Medline][Order article via Infotrieve]
  63. Vanita V, Singh D, Robinson PN, Sperling K, Singh JR. A novel mutation in the DNA-binding domain of MAF at 16q23.1 associated with autosomal dominant "cerulean cataract" in an Indian family. Am J Med Genet A. 2006;140:558–566.[Medline][Order article via Infotrieve]
  64. Bu L, Jin Y, Shi Y, et al. Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract. Nat Genet. 2002;31:276–278.[CrossRef][ISI][Medline][Order article via Infotrieve]
  65. Ott J. A computer program for linkage analysis of general human pedigrees. Am J Hum Genet. 1976;28:528–529.[ISI][Medline][Order article via Infotrieve]
  66. Cottingham RW, Jr, Idury RM, Schaffer AA. Faster sequential genetic linkage computations. Am J Hum Genet. 1993;53:252–263.[ISI][Medline][Order article via Infotrieve]
  67. Lathrop GM, Lalouel JM. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984;36:460–465.[ISI][Medline][Order article via Infotrieve]
  68. Lathrop GM, Lalouel JM, White RL. Construction of human linkage maps: likelihood calculations for multilocus linkage analysis. Genet Epidemiol. 1986;3:39–52.[CrossRef][ISI][Medline][Order article via Infotrieve]
  69. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996;58:1347–1363.[ISI][Medline][Order article via Infotrieve]
  70. National Center For BioTechnology Information (NCBI). National Institutes of Health Bethesda, MD. : http://www.ncbi.nlm.nih.gov/ 2005.
  71. Hubbard T, Barker D, Birney E, et al. The Ensembl genome database project. Nucleic Acids Res. 2002;30:38–41.Available at http://www.ensembl.org/ 2005.[Abstract/Free Full Text]
  72. Girelli D, Corrocher R, Bisceglia L, et al. Molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome: a mutation in the iron-responsive element of ferritin L-subunit gene (the "Verona mutation") (see comments). Blood. 1995;86:4050–4053.[Abstract/Free Full Text]
  73. SeattleSNPs. NHLBI (National Heart, Lung, and Blood Institute) Program for Genomic Applications. 2005; University of Washington, Fred Hutchinson Cancer Research Center Seattle, WA. Available at http://pga.mbt.washington.edu.
  74. Pisano MM, Chepelinsky AB. Genomic cloning, complete nucleotide sequence, and structure of the human gene encoding the major intrinsic protein (MIP) of the lens. Genomics. 1991;11:981–990.[CrossRef][ISI][Medline][Order article via Infotrieve]
  75. Gorin MB, Yancey SB, Cline J, Revel JP, Horwitz J. The major intrinsic protein (MIP) of the bovine lens fiber membrane: characterization and structure based on cDNA cloning. Cell. 1984;39:49–59.[CrossRef][ISI][Medline][Order article via Infotrieve]
  76. Shiels A, Griffin CS. Aberrant expression of the gene for lens major intrinsic protein in the CAT mouse. Curr Eye Res. 1993;12:913–921.[ISI][Medline][Order article via Infotrieve]
  77. Shiels A, Bassnett S. Mutations in the founder of the MIP gene family underlie cataract development in the mouse. Nat Genet. 1996;12:212–215.[CrossRef][ISI][Medline][Order article via Infotrieve]
  78. Sidjanin DJ, Parker-Wilson DM, Neuhauser-Klaus A, et al. A 76-bp deletion in the Mip gene causes autosomal dominant cataract in Hfi mice. Genomics. 2001;74:313–319.[CrossRef][ISI][Medline][Order article via Infotrieve]
  79. Okamura T, Miyoshi I, Takahashi K, et al. Bilateral congenital cataracts result from a gain-of-function mutation in the gene for aquaporin-0 in mice. Genomics. 2003;81:361–368.[CrossRef][ISI][Medline][Order article via Infotrieve]
  80. Geyer DD, Spence MA, Johannes M, et al. Novel single base deletional mutation in major intrinsic protein (MIP) in autosomal dominant cataract. Am J Ophthalmol. 2006;141:761–763.[CrossRef][ISI][Medline][Order article via Infotrieve]
  81. Tenbroek E, Arneson M, Jarvis L, Louis C. The distribution of the fiber cell intrinsic membrane proteins MP20 and connexin46 in the bovine lens. J Cell Sci. 1992;103:245–257.[Abstract/Free Full Text]
  82. Arneson ML, Louis CF. Structural arrangement of lens fiber cell plasma membrane protein MP20. Exp Eye Res. 1998;66:495–509.[CrossRef][ISI][Medline][Order article via Infotrieve]
  83. Kerscher S, Glenister PH, Favor J, Lyon MF. Two new cataract loci, Ccw and To3, and further mapping of the Npp and Opj cataracts in the mouse. Genomics. 1996;36:17–21.[CrossRef][ISI][Medline][Order article via Infotrieve]
  84. Kerscher S, Church RL, Boyd Y, Lyon MF. Mapping of four mouse genes encoding eye lens-specific structural, gap junction, and integral membrane proteins: Cryba1 (crystallin beta A3/A1), Crybb2 (crystallin beta B2), Gja8 (MP70), and Lim2 (MP19). Genomics. 1995;29:445–450.[CrossRef][ISI][Medline][Order article via Infotrieve]
  85. Steele EC, Jr, Kerscher S, Lyon MF, et al. Identification of a mutation in the MP19 gene, Lim2, in the cataractous mouse mutant To3. Mol Vis. 1997;3:5.[Medline][Order article via Infotrieve]
  86. Steele EC, Jr, Wang JH, Lo WK, Saperstein DA, Li X, Church RL. Lim2(To3) transgenic mice establish a causative relationship between the mutation identified in the lim2 gene and cataractogenesis in the To3 mouse mutant. Mol Vis. 2000;6:85–94.[ISI][Medline][Order article via Infotrieve]
  87. Taylor V, Welcher AA, Program AE, Suter U. Epithelial membrane protein-1, peripheral myelin protein 22, and lens membrane protein 20 define a novel gene family. J Biol Chem. 1995;270:28824–28833.[Abstract/Free Full Text]
  88. Zhou L, Li X, Church RL. The mouse lens fiber-cell intrinsic membrane protein MP19 gene (Lim2) and granule membrane protein GMP-17 gene (Nkg7): Isolation and sequence analysis of two neighboring genes. Mol Vis. 2001;7:79–88.[ISI][Medline][Order article via Infotrieve]
  89. Zhou L, Chen T, Church RL. Temporal expression of three mouse lens fiber cell membrane protein genes during early development. Mol Vis. 2002;8:143–148.[ISI][Medline][Order article via Infotrieve]
  90. Pras E, Levy-Nissenbaum E, Bakhan T, et al. A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family. Am J Hum Genet. 2002;70:1363–1367.[CrossRef][ISI][Medline][Order article via Infotrieve]
  91. Davis BM, McCurrach ME, Taneja KL, Singer RH, Housman DE. Expansion of a CUG trinucleotide repeat in the 3' untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts. Proc Natl Acad Sci USA. 1997;94:7388–7393.[Abstract/Free Full Text]
  92. Wang J, Pegoraro E, Menegazzo E, et al. Myotonic dystrophy: evidence for a possible dominant-negative RNA mutation. Hum Mol Genet. 1995;4:599–606.[Abstract/Free Full Text]
  93. Tiscornia G, Mahadevan MS. Myotonic dystrophy: the role of the CUG triplet repeats in splicing of a novel DMPK exon and altered cytoplasmic DMPK mRNA isoform ratios. Mol Cell. 2000;5:959–967.[CrossRef][ISI][Medline][Order article via Infotrieve]
  94. Phillips MF, Rogers MT, Barnetson R, et al. PROMM:the expanding phenotype: a family with proximal myopathy, myotonia and deafness. Neuromuscul Disord. 1998;8:439–446.[CrossRef][ISI][Medline][Order article via Infotrieve]
  95. Mankodi A, Logigian E, Callahan L, et al. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science. 2000;289:1769–1773.[Abstract/Free Full Text]
  96. Otten AD, Tapscott SJ. Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure. Proc Natl Acad Sci USA. 1995;92:5465–5469.[Abstract/Free Full Text]
  97. Klesert TR, Otten AD, Bird TD, Tapscott SJ. Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP. Nat Genet. 1997;16:402–406.[CrossRef][ISI][Medline][Order article via Infotrieve]
  98. Thornton CA, Wymer JP, Simmons Z, McClain C, Moxley RT, 3rd. Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene. Nat Genet. 1997;16:407–409.[CrossRef][ISI][Medline][Order article via Infotrieve]
  99. Klesert TR, Cho DH, Clark JI, et al. Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy. Nat Genet. 2000;25:105–109.[CrossRef][ISI][Medline][Order article via Infotrieve]
  100. Sarkar PS, Appukuttan B, Han J, et al. Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts. Nat Genet. 2000;25:110–114.[CrossRef][ISI][Medline][Order article via Infotrieve]
  101. Winchester CL, Ferrier RK, Sermoni A, Clark BJ, Johnson KJ. Characterization of the expression of DMPK and SIX5 in the human eye and implications for pathogenesis in myotonic dystrophy. Hum Mol Genet. 1999;8:481–492.[Abstract/Free Full Text]
  102. Bonneau D, Winter-Fuseau I, Loiseau MN, et al. Bilateral cataract and high serum ferritin: a new dominant genetic disorder?. J Med Genet. 1995;32:778–779.[ISI][Medline][Order article via Infotrieve]
  103. Cazzola M, Cremonesi L, Papaioannou M, et al. Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3). Br J Haematol. 2002;119:539–546.[CrossRef][ISI][Medline][Order article via Infotrieve]
  104. Curtis AR, Fey C, Morris CM, et al. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet. 2001;28:350–354.[CrossRef][ISI][Medline][Order article via Infotrieve]
  105. Girelli D, Bozzini C, Zecchina G, et al. Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia-cataract syndrome. Br J Haematol. 2001;115:334–340.[CrossRef][ISI][Medline][Order article via Infotrieve]
  106. Lachlan KL, Temple IK, Mumford AD. Clinical features and molecular analysis of seven British kindreds with hereditary hyperferritinaemia cataract syndrome. Eur J Hum Genet. 2004;12:790–796.[CrossRef][ISI][Medline][Order article via Infotrieve]
  107. Phillips JD, Warby CA, Kushner JP. Identification of a novel mutation in the L-ferritin IRE leading to hereditary hyperferritinemia-cataract syndrome (Abstract). Am J Med Genet. A. 2005;134:77–79.[Medline][Order article via Infotrieve]
  108. Riazuddin SA, Yasmeen A, Zhang Q, et al. A new locus for autosomal recessive nuclear cataract mapped to chromosome 19q13 in a Pakistani family. Invest Ophthalmol Vis Sci. 2005;46:623–626.[Abstract/Free Full Text]




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