Original Article
Clinical characteristics and genetic analysis of a pedigree with Stargardt disease caused by a novel mutation in ABCA4 gene
Wang Rongrong, Liu Jingwen, Ma Jingyu, Zhen Qingjie, Lu Zhiming, Bai Xiaohui
Published 2022-12-19
Cite as Chin J Lab Med, 2022, 45(12): 1219-1226. DOI: 10.3760/cma.j.cn114452-20220302-00115
Abstract
ObjectiveTo explore the clinical characteristics and genetics of a pedigree with Stargardt disease, and investigate the pathogenicity of ABCA4 (ATP binding cassette subfamily A member 4) gene mutations in Stargardt disease.
MethodsThe proband was admitted to the Second People′s Hospital of Jinan in May 2021 due to diminution of vision. The proband was diagnosed with Stargardt disease according to the clinical diagnostic criteria of Stargardt disease. Detailed ophthalmological examinations was also performed on family members of the proband. Genomic DNA were extracted from the proband and the family members, and the whole exon sequencing was performed to find pathogenic gene mutations. The hazard of mutations was analyzed by polyphen-2, SIFT and MutationTaster websites. Sanger sequencing was used to verify the mutations. Conserved analysis of homologous species and 3-dimensional (3D) molecular model of the protein were used to analyze the pathogenicity.
ResultsOphthalmological examinations showed reduced binocular vision, macular atrophy and "bull′s eye sign" in the proband and there was no abnormal signs and symptoms among the family members. Through whole exon sequencing analysis and Sanger sequencing verification, the compound heterozygous mutations (c.215G>A and c.6563T>C) of ABCA4 gene were co-segregated with this disease in this family. SIFT, Polyphen-2 and MutationTaster predicted that these two mutations were pathogenic. Conservative analysis and 3D molecular model of protein showed that mutations could cause changes in protein structure and affect protein function.
ConclusionThe compound heterozygous mutations (C.215G>A and C.6563T>C) of ABCA4 gene are the pathogenic mutations of Stargardt disease in this pedigree.
Key words:
Stargardt Disease; ATP-Binding Cassette Transporters; Mutation; Pedigree; Heredity
Contributor Information
Wang Rongrong
Department of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
Liu Jingwen
Department of Ophthalmology, the Second People′s Hospital of Jinan, Jinan 250021, China
Ma Jingyu
Department of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
Zhen Qingjie
Department of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
Lu Zhiming
Department of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
Bai Xiaohui
Department of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan 250021, China
