Mutation Spectrum And Frequency Of 15 Causative Genes In 87 Unrelated Chinese Patients With Leber Congenital Amaurosis

Abstract

Purpose: : Leber congenital amaurosis (LCA) is the earliest and most severe form of hereditary retinal dystrophy causing blindness in infants. So far, the mutation spectrum and frequency of the 15 known causative genes have not been evaluated in East Asians. Therefore, we performed a comprehensive screening in Chinese patients with LCA.

Methods: : Mutation screening of 15 causative genes was performed in 87 unrelated Chinese patients with LCA. The most frequently mutated exons/intron in the 15 genes were selected for the initial mutation scan. Subsequently, all the remaining exons of 10 genes were sequenced for all patients.

Results: : Fifty-one mutations in the 15 known LCA genes were identified in 44 patients (50.6%, 44/87) of patients, involving 77 alleles (11 homozygous and 55 heterozygous) of the 44 patients, Of the 51 mutations, 33(64.6%) were novel pathogenic mutations. Heterozygous and compound heterozygous mutations are more common than homozygous mutations in our population. One patient had digenic mutations and two patients had possible triallelic mutations. Mutations in GUCY2D appeared to be the most common cause of LCA in Chinese patients (16.1% cases), followed by CRB1 (11.5%), RPGRIP1 (8%), RPE65 (5.7%), SPATA7 (4.6%), CEP290 (4.6%), CRX (3.4%), LCA5 (2.3%), AIPL1 (1.1%), and RDH12 (1.1%), which are different from other populations. The mutation detection rate based on the initial scan (50 exons and 1 intron) of selected exons in 15 genes (198 exons and 1 intron) is 83.1% (64/77) mutant alleles.

Conclusions: : Our results demonstrate an ethnic-different mutations spectrum of LCA genes in Chinese population. In addition, sequencing exons with the highest risk in a proper order is a simple and efficient strategy for mutation detection in LCA.

Keywords: retinal degenerations: hereditary • gene screening