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Whole Exome Sequencing in Eight Thai Patients With Leber Congenital Amaurosis Reveals Mutations in the CTNNA1 and CYP4V2 Genes.

Abstract：

Purpose:Our goal was to describe the clinical and molecular genetic findings in Thai patients with Leber congenital amaurosis (LCA). Methods:Whole exome sequencing (WES) was performed in eight unrelated patients. All genes responsible for inherited retinal diseases (IRDs) based on RetNet were selected for analysis. Potentially causative variants were filtered through a bioinformatics pipeline and validated using Sanger sequencing. Segregation analysis of the causative genes was performed in family members when available. Results:Eleven deleterious variants, six nonsense and five missense, were identified in seven genes: four LCA-associated genes (CEP290, IQCB1, NMNAT1, and RPGRIP1), one gene responsible for syndromic LCA (ALMS1), and two IRDs-related genes (CTNNA1 and CYP4V2). Clinical reassessment supported the diagnosis of syndromic LCA in those patients harboring potentially pathogenic variants in the ALMS1. Interestingly, two causative genes, CTNNA1 and CYP4V2, previously reported to cause butterfly-shaped pigment dystrophy (BSPD) and Bietti's crystalline dystrophy (BCD), respectively, were detected in two other patients. These two patients developed rapid and severe visual loss in contrast to BSPD and BCD patients in previous studies. The results of this study demonstrate that causative variants identified in the CTNNA1 and CYP4V2 genes are also associated with LCA. Conclusions:This is the first report describing the molecular genetics and clinical manifestations of Thai patients with LCA. The present study expands the spectrum of LCA-associated genes, which is a benefit for molecular diagnosis. The identification of mutations in the CTNNA1 and CYP4V2 genes requires further elucidation in larger cohorts with LCA.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Jinda W,Taylor TD,Suzuki Y,Thongnoppakhun W,Limwongse C,Lertrit P,Trinavarat A,Atchaneeyasakul LO

doi

10.1167/iovs.16-21322

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

2413-2420

issue

eissn

0146-0404

issn

1552-5783

pii

2624456

journal_volume

pub_type

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Whole Exome Sequencing in Eight Thai Patients With Leber Congenital Amaurosis Reveals Mutations in the CTNNA1 and CYP4V2 Genes.