Novel variants of ABCA4 in Han Chinese families with Stargardt disease

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

1 Scopus Citations
View graph of relations

Author(s)

  • Fang-Yuan Hu
  • Feng-Juan Gao
  • Ping Xu
  • Dan-Dan Wang
  • Sheng-Hai Zhang
  • Ji-Hong Wu

Related Research Unit(s)

Detail(s)

Original languageEnglish
Article number213
Journal / PublicationBMC Medical Genetics
Volume21
Online published31 Oct 2020
Publication statusPublished - 2020

Link(s)

Abstract

Background: Stargardt disease (STGD1) is a common recessive hereditary macular dystrophy in early adulthood or childhood, with an estimated prevalence of 1:8000 to 1:10,000. ABCA4 is the causative gene for STGD1. The current study aims at identifying the novel disease-related ABCA4 variants in Han Chinese families with STGD1 using next-generation sequencing (NGS). 
Methods: In the present study, 12 unrelated Han Chinese families (19 males and 17 females) with STGD1 were tested by panel-based NGS. In order to capture the coding exons and the untranslated regions (UTRs) plus 30 bp of intronic flanking sequences of 792 genes, which were closely associated with usual ophthalmic genetic disease, we designed a customized panel, namely, Target_Eye_792_V2 chip. STGD1 patients were clinically diagnosed by experienced ophthalmologists. All the detected variants were filtered and analyzed through the public databases and in silico programs to assess potential pathogenicity. 
Results: Twenty-one ABCA4 mutant variants were detected in 12 unrelated Han Chinese families with STGD1, containing 14 missense, three splicing, two frameshift, one small deletion, and one nonsense variants. Base on the American College of Medical Genetics (ACMG) guidelines, 8 likely pathogenic and 13 pathogenic variants were determined. The functional consequences of these mutant variants were predicted through in silico programs. Of the 21 mutant variants in ABCA4, two novel coding variants c.3017G > A and c.5167 T > C and one novel null variant c.3051-1G > A were detected in three unrelated probands. 
Conclusions: By panel-based NGS, 21 ABCA4 variants were confirmed in 12 unrelated Han Chinese families. Among them, 3 novel mutant variants were found, which further expanded the ABCA4 mutation spectrum in STGD1 patients.

Research Area(s)

  • ABCA4 gene, Han Chinese patients, Novel mutant variants, Panel-based NGS, STGD1

Citation Format(s)

Novel variants of ABCA4 in Han Chinese families with Stargardt disease. / Hu, Fang-Yuan; Gao, Feng-Juan; Li, Jian-kang; Xu, Ping; Wang, Dan-Dan; Zhang, Sheng-Hai; Wu, Ji-Hong.

In: BMC Medical Genetics, Vol. 21, 213, 2020.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review