The Transcription Factor Gene FOXC1 Exhibits a Limited Role in Primary Congenital Glaucoma
Subhabrata Chakrabarti 1*,
Kiranpreet Kaur 1,
Kollu N Rao 1,
Anil K Mandal 2,
inderjeet Kaur 3,
Rajul S. Parikh 2,
and
Ravi Thomas 4
1 Molecular Genetics, L.V. Prasad Eye Institute, Hyderabad, India
2 V. S. T. Glaucoma Center, L. V. Prasad Eye Institute, hyderabad, India
3 Hyderabad Eye Research Foundation, L V Prasad Eye Institute, Hyderabad, India
4 ophthalmology, Queensland Eye Institute, 41 Annerley Road, , Brisbane, Queensland, 4101, Australia; Glaucoma, Queensland Eye Institute, Brisbane, Australia; V. S. T. Glaucoma Center, L. V. Prasad Eye Institute, hyderabad, India
* To whom correspondence should be addressed. E-mail: subho.chakrabarti{at}gmail.com.
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Abstract |
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Purpose: Primary congenital glaucoma (PCG) is an autosomal recessive disorder that has been linked to CYP1B1 mutations. We aimed to explore the role of FOXC1, which is involved in anterior segment dysgenesis, in PCG.
Methods: Our earlier screening for CYP1B1 in a clinically well characterized PCG cohort (n=301) revealed cases that were either homozygous (n=73), compound heterozygous (n=18) or heterozygous (n=41) for the mutant allele, while the remaining (n=169) did not harbor any mutation. Hence, FOXC1 was screened in 210 PCG cases who were either heterozygous (41) or did not harbor any CYP1B1 mutation (169) along with ethnically matched normal controls (n=157) by resequencing the entire coding region.
Results: Two heterozygous missense (H128R and C135Y) and three frameshift mutations (g.1086delC, g.1155del9bp and g.1947dup25bp) were observed in FOXC1 in 5/210 (2.38%) cases. The missense mutations had a de novo origin in two sporadic cases, while the FOXC1 deletions were seen in two cases that were also heterozygous for the CYP1B1 allele (R368H). The parents of the proband with g.1086delC were heterozygous for either FOXC1 or CYP1B1 alleles. The unaffected mother of the proband with the g.1155del9bp was heterozygous for both the FOXC1 and CYP1B1 alleles; the father harbored only the FOXC1 allele. Familial segregation of the g.1947dup25bp could not be done due to the unavailability of DNA from one of the parent. Except for the g.1155del9bp (0.95% normal chromosomes), all the other variations were absent in the controls.
Conclusion: The present study indicates a limited role of FOXC1 in PCG pathogenesis.
Key Words:
FOXC1, genetic diseases, glaucoma, CYP1B1, Gene, Mutations
