Clinical exome sequencing facilitates the understanding of genetic heterogeneity in Leber congenital amaurosis patients with variable phenotype in southern India

作     者：Sriee Viswarubhiny Rupa Anjanamurthy Ayyasamy Vanniarajan Devarajan Bharanidharan Vijayalakshmi Perumalsamy Periasamy Sundaresan 

作者机构：Department of Molecular GeneticsAravind Medical Research FoundationAravind Eye HospitalMaduraiTamil Nadu 625020India Department of Molecular BiologyAravind Medical Research Foundation-Affiliated to Alagappa UniversityKaraikudiTamil NaduIndia Department of Paediatric and Adult strabismusAravind Eye HospitalMaduraiTamil NaduIndia Department of BioinformaticsAravind Medical Research FoundationAravind Eye HospitalMaduraiTamil NaduIndia 

出 版 物：《Eye and Vision》 (眼视光学杂志（英文）)

年 卷 期：2021年第8卷第1期

页      面：192-202页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：supported by the Department of Biotechnology under Grant BT/NNT/28/SP18830/2018 

主　　题：Leber congenital amaurosis Clinical exome sequencing Southern India Molecular diagnosis Genotype-phenotype correlation 

摘      要：Background:Leber congenital amaurosis(LCA),primarily characterized by retinal degeneration is the most severe form of inherited retinal dystrophy(IRD)responsible for congenital *** presence of phenotypic heterogeneity makes the diagnosis of LCA challenging,especially in the absence of pronounced disease pathognomonic,yet it can be well comprehended by employing molecular ***,the present study aimed to reveal the causative mutations in ten LCA patients with variable phenotypes using clinical exome sequencing(CES).Methods:CES was performed in ten unrelated LCA *** information and family history of all patients were obtained to make a meaningful *** clinical exome data was analyzed and prioritized using a bioinformatics pipeline to identify mutations,which was further validated by Sanger *** analysis was also performed on available family ***:CES led to the identification of causative mutations in nine LCA *** patients harbored a mutation in six LCA candidate genes,including RPE65,LCA5(n=2),CRX,PRPH2,CEP290,and ALMS1,while two patients possess a mutation in IFT80 and RP1,known to cause other *** novel mutations in LCA5(c.1823del),CRX(c.848del)and CEP290(c.2483GT)were *** current study reports for the first time,a mutation in PRPH2,CEP290,and ALMS1 from the Indian ***,we observed a novel association of LCA phenotype with IFT80 known to cause Jeune *** on the genetic finding,the patient AS09,who harbored a mutation in the RP1 gene,was re-diagnosed with early-onset retinitis ***:In conclusion,the results underline the importance of CES in clinically diagnosed LCA patients with variable *** correlation between mutations in candidate genes and clinical phenotypes,helps to refine the clinical ***,molecular evaluation with a larger cohort of LCA patients is needed for better understa