IOVS Biophysical Journal
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Griesinger, I. B.
Right arrow Articles by Ayyagari, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Griesinger, I. B.
Right arrow Articles by Ayyagari, R.
(Investigative Ophthalmology and Visual Science. 2000;41:248-255.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

Autosomal Dominant Macular Atrophy at 6q14 Excludes CORD7 and MCDR1/PBCRA Loci

Irina B. Griesinger, Paul A. Sieving and Radha Ayyagari

From the W. K. Kellogg Eye Center, University of Michigan, Ann Arbor.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
PURPOSE. Localization of the gene responsible for autosomal dominant atrophic macular degeneration (adMD) in a large pedigree UM:H785.

METHODS. Standard ophthalmologic examinations were performed. Microsatellite markers were used to map the disease gene by linkage and haplotype analyses.

RESULTS. The macular degeneration in this family is characterized by progressive retinal pigment epithelial atrophy in the macula without apparent peripheral involvement by ophthalmoscopy or functional studies. Acuity loss progressed with age and generally was worse in the older affected individuals. The rod and cone function remained normal or nearly normal in all tested affected members up to 61 years of age. The phenotype in our family has characteristics similar to Stargardt-like macular degeneration with some differences. Haplotype analysis localized the disease gene in our adMD family to an 8-cM region at 6q14, which is within the 18-cM interval of STGD3 but excludes cone-rod dystrophy 7 (CORD7; centromeric) and North Carolina macular degeneration and progressive bifocal chorioretinal atrophy (MCDR1/PBCRA; telomeric). The mapping interval overlaps with that of recessive retinitis pigmentosa (RP25).

CONCLUSIONS. These results implicate at least three genetically distinct loci for forms of macular degeneration that lie within a 30-cM interval on chromosome 6p11–6q16: CORD7, adMD, and MCDR1/PBCRA. Because the critical interval for the adMD family studied overlaps with STGD3 and RP25, these loci could be allelic.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Macular degenerations are a heterogeneous group of disorders that affect function of the sensory retina, retinal pigment epithelium (RPE) of the macula, or both and result in reduced visual acuity. More than 30 genetically distinct macular disorders have been described.1 Color vision is impaired in some forms of macular degeneration, particularly those designated as involving cone degeneration. Mutations in some of these genes cause a broad phenotype spectrum and can also affect peripheral retinal function and thereby mimic retinal degeneration, as occurs with some RDS/peripherin mutations.2

We studied a five-generation pedigree (family UM:H785) with atrophic macular degeneration that follows autosomal dominant (ad) inheritance and maps to chromosome 6q14. The condition bears some resemblance to recessive Stargardt disease but without the dark fluorescein angiogram frequently found in that condition.3 Several other forms of retinal/macular degenerations have been mapped to the pericentromeric region of chromosome 6 including an autosomal dominant condition termed Stargardt-like macular degeneration (Fig. 4) .4 5 6 7 8 9 10 11 The disease-causing gene locus in our family could be allelic to one or more of those conditions.



View larger version (21K):
[in this window]
[in a new window]
  		Figure 4. Schematic shows the retinal disease genes that map to the long arm of chromosome 6. The critical interval of RP25 extends to the 6p.16

 
By linkage and haplotype analysis, we excluded the cone-rod dystrophy 7 (CORD7), North Carolina macular degeneration (MCDR1), and progressive bifocal chorioretinal atrophy (PBCRA) loci from the disease gene interval of our adMD family. As a consequence, our data demonstrate that there must be at least three genetically independent loci for forms of macular degeneration within the 30-cM interval on 6p11–6q16. We describe the phenotype of this family and present the genetic interval for this condition.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Examinations were performed on 10 affected and 4 unaffected members, 15 to 67 years of age, in pedigree UM:H785 (Fig. 1) , with informed consent in conjunction with molecular genetic analysis. The research followed the tenets of the Declaration of Helsinki. Visual fields were determined by Goldmann perimetry using white targets. Color vision was tested with Ishihara plates and the Farnsworth D-15 color panel.12 Rod absolute threshold sensitivities were determined at six loci across the horizontal meridian using a Goldmann-Weekers dark adaptometer after 1 hour of dark-adaptation. The Ganzfeld electroretinogram (ERG) was recorded at 0.1 to 1000 Hz (-3 dB) with bipolar contact lens electrodes after full pupillary dilation. Normal values from 50 control subjects 8 to 65 years of age were as follows: scotopic rod b-wave mean = 325 µV (SD = 82, min >= 204 µV), elicited by 0.5-Hz dim blue (440-nm peak, 70-nm half-width) stimuli at -1.86 log cd-s/m2; photopic cone b-wave mean = 124 µV (SD = 36, min >= 56 µV), elicited by 0.5-Hz "white" flashes (0.62 log cd-s/m2) on a 43-cd/m2 background; and cone 30-Hz flicker response mean = 92 µV (SD = 31, min >= 52 µV) and implicit times <=32 msec, for 30-Hz "white" stimuli of 0.62 log cd-s/m2 per flash.



View larger version (56K):
[in this window]
[in a new window]
  		Figure 1. Autosomal dominant macular degeneration pedigree UM:H785 and haplotypes with 16 microsatellite markers on chromosome 6q. Squares and circles indicate males and females, respectively. Filled symbols signify affected individuals, and open symbols indicate unaffected family members. A plus sign (+) indicates that a fluorescein angiogram was obtained. Filled bars indicate the disease haplotype. Question marks in the haplotype denote polymerase chain reaction amplification failure.

 
Genotyping
Blood samples were obtained from 24 family members and 6 spouses, and leukocyte DNA was extracted. Genotyping was performed as described previously.13 The PCR products were separated by denaturing gel electrophoresis and visualized by autoradiography. Descriptions of the polymorphic markers and genetic distances were obtained from the Genome Database (http://gdb.wehi.edu.au/gdb/gdbtop.html).

Linkage Analysis
Two point linkage analysis was performed between the disease gene and each marker using the MLINK program (version 5.1) of the LINKAGE package.14 The disease was coded as a fully penetrant autosomal dominant trait with a gene frequency of 0.00001 for the affected allele. Marker allele frequencies given in the Genome Database were used.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Clinical Description
Pedigree UM:H785 (Fig. 1) has atrophic macular degeneration that follows autosomal dominant inheritance, with individuals affected in five consecutive generations and male-to-male transmission. Clinical features of 10 affected individuals are summarized in Table 1 . Some individuals were affected by teenage years. Acuity loss progressed with age, and the older affected members generally had worse symptoms. The peripheral retina normally was spared on visual field testing, and full-field ERG function was normal or nearly normal across all ages tested up to 61 years of age. This was not a primary cone dystrophy, as judged by nearly normal color vision and cone ERGs (Fig. 2) .


View this table:
[in this window]
[in a new window]
  		Table 1. Clinical Findings of Atrophic–6q14–adMD in Family UM:H785

 


View larger version (30K):
[in this window]
[in a new window]
  		Figure 2. ERG of eight affected individuals in atrophic-6q14-adMD pedigree UM:H785. The rod and cone ERG amplitudes are normal on all, except for 30-Hz flicker for two affected individuals who had slightly subnormal amplitudes (VI:2 and V:2) and two who had minimal implicit time delays (IV:6 and IV:2). y/o, years old.

 
As an example of typical findings of affected individuals in this family, female IV:6 had visual acuities of 20/70 in both eyes at 42 years of age that decreased to 20/200 several years later. However, her color vision remained good throughout this time, with 13 of 14 Ishihara plates identified correctly with either eye. Both maculae showed central atrophy surrounded by yellowish "flecks," and "window defect" clusters were seen on the fluorescein angiogram (Fig. 3F ). Peripheral retinal function was spared as judged by normal visual fields even with the small I4e Goldmann target, normal full-field rod dark-adapted sensitivities, and normal cone ERG responses except for a slight delay of the 30-Hz flicker implicit time to 34 msec (Fig. 2) . RPE integrity was good as judged by normal electro oculogram (EOG) Arden ratios of 2.2 right eye and 2.1 left eye.



View larger version (128K):
[in this window]
[in a new window]
  		Figure 3. Fluorescein angiogram of 10 male (M) and female (F) affected individuals, 15 to 61 years of age (y/o), in pedigree UM:H785. Corresponding individual number and age are shown below each angiogram. All show hyperfluorescent "window defects" in the macula. The angiograms all tend to be darker than normal, but none has a jet-black "dark, silent choroid."

 
As shown in Table 1 , ERGs were performed on eight affected individuals (Fig. 2) , and all had normal scotopic and photopic b-wave amplitudes. Cone 30-Hz flicker amplitudes were normal in six and minimally subnormal in two; two others had slightly prolonged implicit times of 33 to 34 msec.

Color vision for all affected individuals except one was very good or normal and did not correlate with acuity loss, as exemplified by affected male V:10 with 20/200 OD and 20/70 OS who made no errors on the D-15 test and identified correctly all 14 Ishihara plates with each eye. VI:9 was a congenital deuteranomalous male on the D-15 test. Only the severely affected 57-year-old woman (V:19) with extensive chorioretinal atrophy was unable to perform color vision testing (Table 1) .

Fluorescein angiograms showed parafoveal "window defects" as an early sign of disease (Figs. 3A 3B 3C 3D 3E) , progressing to geographic macular atrophy in later stages (Figs. 3I 3J) . Most affected fundi showed peripapillary RPE atrophy. All showed slight darkening of the fluorescein angiogram background, but none had the stark black "dark choroid" that can be observed in recessive Stargardt macular degeneration.

Results of Linkage and Haplotype Analysis
We localized this condition to chromosome 6, and markers tightly linked to retinal disease loci on this chromosome were studied further. Analysis of marker D6S271, which is linked to RDS/peripherin4 and markers D6S275/D6S300, which are tightly linked to MCDR1/PBCRA,9 11 15 gave two-point LOD scores of -{infty} at 0.0 recombination fraction. Marker D6S280, which is linked with Stargardt-like macular degeneration,6 gave an LOD score of 4.48 at theta = 0.05 (Table 2) . A systematic analysis was then performed by genotyping more than 40 markers between D6S402 and D6S300. The results of two-point linkage analysis with selected markers in the critical region are shown in Table 2 . The maximum LOD score of 6.55 was obtained with marker D6S1609 at 0.0 recombination. Six markers between D6S1625 and D6S1613 gave significant positive LOD scores (>3.0) at zero recombination, thus localizing the macular degeneration in this family to 6q14 (Table 2) .


View this table:
[in this window]
[in a new window]
  		Table 2. Two point LOD scores of microsatellite markers on chromosome 6 vs family UM:H785

 
Figure 1 shows the haplotypes for this family. MCDR1 and PBCRA have been localized telomeric to D6S300. Affected individual V:19 and her affected son (VI:9) show recombination at D6S275. They carry the normal haplotype telomeric to this marker and thereby exclude the MCDR1/PBCRA loci from the disease gene interval in this family. The unaffected son (VI:8; age, 38 years) carries the affected haplotype between markers D6S1644 and D6S275, which places the disease-causing gene further centromeric of D6S1613. These haplotypes place the adMD locus in family UM:H785 centromeric to the published interval for MCDR1 and PBCRA (Fig. 4) .9 11 15 The interval for CORD7 has been mapped between markers D6S430 and D6S1625.8 Unaffected individual V:14 (age 38 years) carries the disease haplotype centromeric to D6S1707, thereby excluding the CORD7 locus from the critical region in our adMD family UM:H785. Individuals (VI:8 and V:14) underwent complete clinical examination at 38 years of age, and no abnormalities were found by ophthalmoscopy or functional testing. Both had normal fluorescein angiograms, and neither showed even early or subtle angiographic changes in the macula. The six affected family members who were seen before 40 years of age had disease changes that were easily seen on the fluorescein angiogram, even for those in their teenage years (Fig. 3) . This haplotype analysis identifies D6S1625 and D6S1613 as the flanking markers and localizes the disease-causing gene to an 8-cM region on 6q14. These results indicate that there is a third locus for macular degeneration on chromosome 6q, which is genetically distinct from CORD7 and MCDR1/PBCRA (Fig. 4) .


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
The gene for macular degeneration in this adMD family is localized to an 8-cM region on chromosome 6q14. This is within the 18-cM interval of STGD3 but excludes CORD7, MCDR1/PBCRA, and RDS/peripherin from the critical region. The 8-cM critical interval in this family overlaps the 16-cM region of RP25. RP25 is autosomal recessive and has "typical RP symptoms ... [with] ... nothing detectable by scotopic ERG,"5 which is quite different from our family (Table 3) .


View this table:
[in this window]
[in a new window]
  		Table 3. Comparison of the Clinical Phenotype of Retinal Macular Dystrophies Mapped to Chromosome 6q

 
CORD7 lies immediately centromeric but is excluded from the critical interval of our family. CORD7 initially shows "bull’s eye" maculopathy but progresses to advanced disease with highly attenuated rod and cone ERG responses unlike our family (Table 3) .8 Both MCDR1 and PBCRA lie telomeric to the critical interval of our family9 10 11 and have phenotypes different from our family. MCDR1 generally is not progressive, at least for grade 1 changes.10 PBCRA shows extensive involvement of the nasal retina and has significant ERG abnormalities unlike our family (Table 3) .16 The RDS/peripherin gene and the guanylate cyclase activator-1A (COD3) gene are both distant, at 6p12-p21.4 17 The mapping interval in a pedigree with Leber phenotype of severe, global, early-age vision loss spans a 64-cM interval that overlaps 6q14,18 but this phenotype is quite different from our family.

The closest phenotype similarity with our family is Stargardt-like dominant macular degeneration,6 which maps to a larger overlapping interval at 6q12–6q14. Stargardt-like macular degeneration causes considerable visual loss before 30 years of age and has progressive color vision loss proportional to the visual acuity reductions.6 Although this seemingly is more severe than in our family, these could be allelic differences or could indicate involvement of separate genes.

Histopathology on Stargardt macular degeneration shows accumulation of lipofuscin in RPE cells.19 Accumulation of lipofuscin was also observed in Sorsby fundus dystrophy and Best macular degeneration.20 21 22 Genes implicated in causing Stargardt, Sorsby, and Best macular degeneration have been identified as ATP-binding cassette transporter (ABCR), tissue inhibitor of metalloproteinases-3 (TIMP-3), and Bestrophin, respectively.23 24 25 Although the mechanisms of these diseases are not understood yet, the products of those genes all seem to be involved in maintaining cellular integrity or dynamics. It has been speculated that the accumulation of lipofuscin in these diseases could result from accelerated turnover of photoreceptor cells; increased phagocytosis of photoreceptor outer segments; abnormal photoreceptor membranes or contents rendered indigestible by the RPE; missing or mutated degradative enzymes capable of digesting photoreceptor proteins or lipids; or failed mechanism to expel lipofuscin from the cytoplasm of RPE.19 24 26 27 Genes or gene products involved in any of the above mechanisms that localize to the critical interval of D6S1625–D6S1613 on chromosome 6q would be good candidates for the macular degeneration in family UM:H785. Thus, genes homologous to ABCR, TIMP-3,and Bestrophin and located within the UM:H785 critical interval should be considered as candidates for mutation analysis in family UM:H785. Our search of the human expressed-sequence database at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/cgi-bin/UniGene/) identified 115 ESTs and 16 known genes in the D6S1625–D6S1613 interval. None of these belong to the ABCR or TIMP3 family or are homologous to Bestrophin.

The phenotype in this family is similar to STGD3, which has been reported to be allelic to CORD7.6 7 8 Our exclusion of the CORD7 and MCDR1/PBCRA loci from the critical interval for our family UM:H785 indicates that there are at least three retinal/macular degeneration loci within 30 cM on chromosome 6 (Fig. 4) . This may signify a grouping of genes that is functionally related in a fashion similar to the HLA genes on chromosome 6p.28 Diseases mapped to overlapping genetic interval (as is the case for STGD3, RP25, and our adMD family UM:H785) could be allelic variants of a single gene, as has been reported for RDS/peripherin phenotypes.2 29 This can be resolved only after the genes have been cloned.


   Acknowledgements
 
The authors thank Bradley B. Nelson, Caraline L. Coats, and Jennifer A. Kemp for their help in preparing the figures.


   Footnotes
 
Supported by NIH/NEI Vision CORE Grant EY07003 (Bethesda, Maryland); NIH/NEI Grant R01-EY-06094, M01RR00042 (Bethesda, Maryland); and grants from the Foundation Fighting Blindness (Hunt Valley, Maryland).

Submitted for publication May 7, 1999; revised August 17, 1999; accepted August 30, 1999.

Commercial relationships policy: N.

Corresponding author: Radha Ayyagari, W. K. Kellogg Eye Center, University of Michigan, 1000 Wall Street, Room 325, Ann Arbor, MI 48105. ayyagari{at}umich.edu


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Mah, DY, Wong, PW, Edwards, A, MacDonald, IM (1998) Recent advances in the genetics of macular dystrophies Can J Ophthalmol 33,135-143[Medline][Order article via Infotrieve]
  2. Weleber, RG, Carr, RE, Murphey, WH, Sheffield, VC, Stone, EM (1993) Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene Arch Ophthalmol 111,1531-1542[Abstract/Free Full Text]
  3. Uliss, AE, Moore, AT, Bird, AC (1987) The dark choroid in posterior retinal dystrophies Ophthalmology 94,1423-1427[Medline][Order article via Infotrieve]
  4. Payne, AM, Downes, SM, Bessant, DA, Bird, AC, Bhattacharya, SS (1998) Founder effect, seen in the British population, of the 172 peripherin/RDS mutation and further refinement of genetic positioning of the peripherin/RDS gene Am J Hum Genet 62,192-195[Medline][Order article via Infotrieve]
  5. Ruiz, A, Borrego, S, Marcos, I, Antinolo, G. (1998) A major locus for autosomal recessive retinitis pigmentosa on 6q, determined by homozygosity mapping of chromosomal regions that contain gamma-aminobutyric acid-receptor clusters Am J Hum Genet 62,1452-1459[Medline][Order article via Infotrieve]
  6. Stone, EM, Nichols, BE, Kimura, AE, Weingeist, TA, Drack, A, Sheffield, VC (1994) Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q Arch Ophthalmol 112,765-772[Abstract/Free Full Text]
  7. Edwards, OA, Miedziak, A, Vrabec, T, et al (1999) Autosomal dominant Stargardt-like macular dystrophy, I: clinical characterization, longitudinal follow-up, and evidence for a common ancestry in families linked to chromosome 6q14 [abstract] Am J Ophthalmol 127,426-435[Medline][Order article via Infotrieve]
  8. Kelsell, RE, Gregory–Evans, K, Gregory, CY, et al (1998) Localization of a gene (CORD7) for a dominant cone-rod dystrophy to chromosome 6q Am J Hum Genet 63,274-279[Medline][Order article via Infotrieve]
  9. Kelsell, RE, Godley, BF, Evans, K, et al (1995) Localization of the gene for progressive bifocal chorioretinal atrophy (PBCRA) to chromosome 6q Hum Mol Genet 4,1653-1656[Abstract/Free Full Text]
  10. Small, KW, Weber, JL, Roses, A, Lennon, F, Vance, JM, Pericak–Vance, MA (1992) North Carolina macular dystrophy is assigned to chromosome 6 Genomics 13,681-685[Medline][Order article via Infotrieve]
  11. Sauer, CG, Schworm, HD, Ulbig, M, et al (1997) An ancestral core haplotype defines the critical region harbouring the North Carolina macular dystrophy gene (MCDR1) J Med Genet 34,961-966[Abstract/Free Full Text]
  12. Birch, JM, Chisholm, IA, Kinnear, P, et al (1979) Clinical testing methods Pokorny, J Smith, VC Verriest, G Pinckers, AJLG eds. Congenital and Acquired Color Vision Defects ,83-135 Academic Press London.
  13. Padma, T, Ayyagari, R, Murty, JS, et al (1995) Autosomal dominant zonular cataract with sutural opacities localized to chromosome 17q11–12 Am J Hum Genet 57,840-845[Medline][Order article via Infotrieve]
  14. Lathrop, GM, Lalouel, JM (1984) Easy calculations of lod scores and genetic risks on small computers Am J Hum Genet 36,460-465[Medline][Order article via Infotrieve]
  15. Small, KW, Puech, B, Mullen, L, Yelchits, S. (1997) North Carolina macular dystrophy phenotype in France maps to the MCDR1 loucs Mol Vis 3,1[Medline][Order article via Infotrieve]
  16. Godley, BF, Tiffin, PA, Evans, K, Kelsell, RE, Hunt, DM, Bird, AC (1996) Clinical features of progressive bifocal chorioretinal atrophy: a retinal dystrophy linked to chromosome 6q Ophthalmology 103,893-898[Medline][Order article via Infotrieve]
  17. Payne, AM, Downes, SM, Bessant, DA, et al (1998) A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1 Hum Mol Genet 7,273-277[Abstract/Free Full Text]
  18. Dharmaraj, S, Robitaille, JM, Zhu, D, Li, YY, Maumenee, IH. (1998) An additional locus for Leber’s congenital amaurosis maps to chromosome 6 [ARVO Abstract] Invest Ophthalmol Vis Sci 39(4),S296Abstract nr 1354
  19. Lopez, PF, Maumenee, IH, de la Cruz, Z, Green, WR (1990) Autosomal-dominant fundus flavimaculatus: clinicopathologic correlation Ophthalmology 97,798-809[Medline][Order article via Infotrieve]
  20. Sorsby, A, Mason, ME, Gardener, N. (1949) A fundus dystrophy with unusual features Br J Ophthalmol 33,67-97[Free Full Text]
  21. Capon, MR, Marshall, J, Krafft, JI, Alexander, RA, Hiscott, PS, Bird, AC (1989) Sorsby’s fundus dystrophy: a light and electron microscopic study Ophthalmology 96,1769-1777[Medline][Order article via Infotrieve]
  22. Vail, D, Shoch, D. (1965) Hereditary degeneration of the macula, II: follow-up report and histopathologic study Trans Am Ophthalmol Soc 63,51-63[Medline][Order article via Infotrieve]
  23. Allikmets, R, Singh, N, Sun, H, et al (1997) A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy Nat Genet 15,236-246[Medline][Order article via Infotrieve]
  24. Weber, BH, Vogt, G, Pruett, RC, Stohr, H, Felbor, U. (1994) Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby’s fundus dystrophy Nat Genet 8,352-356[Medline][Order article via Infotrieve]
  25. Petrukhin, K, Kiosti, MJ, Bakall, B, et al (1998) Identification of the gene responsible for Best macular dystrophy Nat Genet 19,241-247[Medline][Order article via Infotrieve]
  26. Weng, J, Mata, NL, Azarian, SM, Tzekov, RT, Birch, DG, Travis, GH (1999) Insights into the function of rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice Cell 98,13-23[Medline][Order article via Infotrieve]
  27. Birnbach, CD, Jarvelainen, M, Possin, DE, Milam, AH (1994) Histopathology and immunocytochemistry of the neurosensory retina in fundus flavimaculatus Ophthalmology 101,1211-1219[Medline][Order article via Infotrieve]
  28. Powis, SH, Geraghty, DE (1995) What is the MHC? Immunol Today 16,466-468[Medline][Order article via Infotrieve]
  29. Wells, J, Wroblewski, J, Keen, J, et al (1993) Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy Nat Genet 3,213-218[Medline][Order article via Infotrieve]



This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
V. Vasireddy, Y. Uchida, N. Salem Jr, S. Y. Kim, M. N. A. Mandal, G. B. Reddy, R. Bodepudi, N. L. Alderson, J. C. Brown, H. Hama, et al.
Loss of functional ELOVL4 depletes very long-chain fatty acids (>=C28) and the unique {omega}-O-acylceramides in skin leading to neonatal death
Hum. Mol. Genet., March 1, 2007; 16(5): 471 - 482.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
V. Vasireddy, M. M. Jablonski, M. N. A. Mandal, D. Raz-Prag, X. F. Wang, L. Nizol, A. Iannaccone, D. C. Musch, R. A. Bush, N. Salem Jr, et al.
Elovl4 5-bp-Deletion Knock-in Mice Develop Progressive Photoreceptor Degeneration.
Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4558 - 4568.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. Raz-Prag, R. Ayyagari, R. N. Fariss, M. N. A. Mandal, V. Vasireddy, S. Majchrzak, A. L. Webber, R. A. Bush, N. Salem Jr, K. Petrukhin, et al.
Haploinsufficiency Is Not the Key Mechanism of Pathogenesis in a Heterozygous Elovl4 Knockout Mouse Model of STGD3 Disease.
Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3603 - 3611.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. Maugeri, F. Meire, C. B. Hoyng, C. Vink, N. Van Regemorter, G. Karan, Z. Yang, F. P. M. Cremers, and K. Zhang
A Novel Mutation in the ELOVL4 Gene Causes Autosomal Dominant Stargardt-like Macular Dystrophy
Invest. Ophthalmol. Vis. Sci., December 1, 2004; 45(12): 4263 - 4267.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
M Michaelides, D M Hunt, and A T Moore
The genetics of inherited macular dystrophies
J. Med. Genet., September 1, 2003; 40(9): 641 - 650.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. C. Khani, A. J. Karoukis, J. E. Young, R. Ambasudhan, T. Burch, R. Stockton, R. A. Lewis, L. S. Sullivan, S. P. Daiger, E. Reichel, et al.
Late-Onset Autosomal Dominant Macular Dystrophy with Choroidal Neovascularization and Nonexudative Maculopathy Associated with Mutation in the RDS Gene
Invest. Ophthalmol. Vis. Sci., August 1, 2003; 44(8): 3570 - 3577.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
P. S. Lagali, J. Liu, R. Ambasudhan, L. E. Kakuk, S. L. Bernstein, G. M. Seigel, P. W. Wong, and R. Ayyagari
Evolutionarily Conserved ELOVL4 Gene Expression in the Vertebrate Retina
Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 2841 - 2850.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Ophthalmol.Home page
P J Francis, S Johnson, B Edmunds, R E Kelsell, E Sheridan, C Garrett, G E Holder, D M Hunt, and A T Moore
Genetic linkage analysis of a novel syndrome comprising North Carolina-like macular dystrophy and progressive sensorineural hearing loss
Br. J. Ophthalmol., July 1, 2003; 87(7): 893 - 898.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
P. S. Bernstein, J. Tammur, N. Singh, A. Hutchinson, M. Dixon, C. M. Pappas, N. A. Zabriskie, K. Zhang, K. Petrukhin, M. Leppert, et al.
Diverse Macular Dystrophy Phenotype Caused by a Novel Complex Mutation in the ELOVL4 Gene
Invest. Ophthalmol. Vis. Sci., December 1, 2001; 42(13): 3331 - 3336.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. O. Edwards, L. A. Donoso, and R. Ritter III
A Novel Gene for Autosomal Dominant Stargardt-like Macular Dystrophy with Homology to the SUR4 Protein Family
Invest. Ophthalmol. Vis. Sci., October 1, 2001; 42(11): 2652 - 2663.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
Y. Li, I. Marcos, S. Borrego, Z. Yu, K. Zhang, and G. Antinolo
Evaluation of the ELOVL4 gene in families with retinitis pigmentosa linked to the RP25 locus
J. Med. Genet., July 1, 2001; 38(7): 478 - 480.
[Full Text]

Home page
 Arch OphthalmolHome page
K. W. Small
Once Again High Tech Meets Low Tech on Chromosome 6
Arch Ophthalmol, April 1, 2001; 119(4): 573 - 575.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Griesinger, I. B.
Right arrow Articles by Ayyagari, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Griesinger, I. B.
Right arrow Articles by Ayyagari, R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS