Purchase this article with an account.
Yang Li, KE XU, Xiaohui Zhang, YUE XIE, FENG JIANG, LIJUAN LIU; Comprehensive Molecular Screening in a cohort of Chinese patients with Leber Congenital Amaurosis or Severe early childhood onset retinal dystrophy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):666.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Leber congenital amaurosis (LCA) and severe early childhood onset retinal dystrophy (SEORD) are clinically and genetically heterogeneous inherited retinal disorders that cause severe visual impairment in children. The objective of this study was to describe the mutation spectrum in a cohort of Chinese patients with LCA or SEORD.
A total of 80 probands were recruited for genetic analysis; these included 39 patients diagnosed with LCA and 41 individuals with SEORD. All patients were firstly screened by deep exome sequencing with a capture panel, which enriches the entire coding exons and splicing site of 171 known retinal disease genes. Then genetic variants were validated by Sanger-DNA sequencing and co-segregation analysis in their family’s members.
We found homozygous or compound heterozygous mutations in 44 unrelated patients, heterozygous autosomal dominant mutations in 7 probands, and X-linked hemizygous mutations in three patients; giving an overall mutation detection rate 67.5% (54/80). In addition, only one heterozygous presumed pathogenic mutation was identified in 19 patients and no mutation was detected in 7 patients. We detected 101 different mutations in 27 genes, which included 70 novel mutations. The identified mutations included 52 (51.5%) missense, 24 (23.8%) nonsense, 7 (6.9%) splicing effect, and 18 (17.8%) frame-shift small insertion or deletion mutations. Of the101 mutations, 87 occurred only once among all 118 mutant alleles (87/118, 73.7%), followed by 12 occurred two times (24/118, 20.3%). The remaining two frequent mutations (occurring three times or more) only accounted for 5.9% (7/118) of all mutant alleles. The first three frequently mutated genes were the RPE65 (15%), RDH12 (13%), and GUCY2D and CRB1 (both 9%) in all the patients of this cohort; while, these were GUCY2D (18%), CEP290 (14%), and CRX (14%) in the LCA patients; RDH12 (25%), CRB1 (15%), and RPE65 (15%) in the SEORD patients (Figure 1).
Our results expanded mutation spectrum of the genes responsible for LCA or SEORD. The most frequently mutated genes in LCA are quite different from the ones of SEORD in this Chinese cohort and are also different from the ones of Caucasian LCA.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Figure 1. Frquencies of the mutated genes in the all patients, LCA patients, and SEORD patients in this Chinese cohort.
This PDF is available to Subscribers Only