Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease
Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease
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中国汉族 Stargardt 病家族新致病性 ABCA4 变异的鉴定
DOI：
10.1042/bsr20180872
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发表时间：
2019-01-31
影响因子：
4
通讯作者：
Deng, Hao
中科院分区：
文献类型：
--
作者：
Xiang, Qin;Cao, Yanna;Deng, Hao
Stargardt disease (STGD1, OMIM 248200) is a common hereditary juvenile or early adult onset macular degeneration. It ultimately leads to progressive central vision loss. Here, we sought to identify gene mutations associated with STGD1 in a three-generation Han Chinese pedigree by whole exome sequencing and Sanger sequencing. Two novel potentially pathogenic variants in a compound heterozygous state, c.3607G > T (p.(Gly1203Trp)) and c.6722T > C (p.(Leu2241Pro)), in the ATP binding cassette subfamily A member 4 gene (ABCA4) were identified as contributing to the family's STGD1 phenotype. These variants may impact the ABCA4 protein structure and reduce the retinal-activated ATPase activity, leading to abnormal all-trans retinal accumulation in photoreceptor outer segments and in retinal pigment epithelium cells. The present study broadens the mutational spectrum of the ABCA4 responsible for STGD1. A combination of whole exome sequencing and Sanger sequencing is likely to be a time-saving and cost-efficient approach to screen pathogenic variants in genetic disorders caused by sizable genes, as well as avoiding misdiagnosis. These results perhaps refine genetic counseling and ABCA4-targetted treatments for families affected by STGD1.
