Analysis of BEST1 gene mutation and clinical phenotype in two families with Best vitelliform macular dystrophy and autosomal recessive bestrophinopathy
10.3760/cma.j.cn511434-20210802-00413
- VernacularTitle:Best卵黄样黄斑营养不良及常染色体隐性卵黄样黄斑营养不良家系 BEST1基因突变及临床表型分析
- Author:
Meng PAN
1
;
Kunpeng XIE
;
Liping DU
;
Pengyi ZHOU
;
Xuemin JIN
Author Information
1. 郑州大学第一附属医院 河南省眼科医院 河南省眼免疫与视网膜损伤及修复国际联合研究实验室 450052
- Keywords:
Vitelliform macular dystrophy;
BEST1 gene mutation
- From:
Chinese Journal of Ocular Fundus Diseases
2021;37(11):841-847
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To report the BEST1 gene mutations and clinical phenotypes in two pedigrees with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). Methods:A retrospective clinical study. From November 2019 to March 2021, in the Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University, the BVMD family (4 patients and 6 family members) and the ARB family (2 patients, 2 family members), a total of 6 patients and 8 normal family members were included in the study. Detailed medical history was obtained; best corrected visual acuity, fundus color photography, electrophysiology, optical coherence tomography and fundus autofluorescence examination were performed. The clinical characteristics for all patients in the two families were analyzed. Three milliliter peripheral venous blood of all participants in the family was collected, and the whole genomic DNA was extracted with gene sequencing using next-generation sequencing technology based on targeted capture. Compared with the database to identify the pathogenicity mutation sites, suspected pathogenic mutation sites were selected, then mutations in other members in the family was assayed by Sanger sequencing.Results:In family 1, the proband was demonstrated as typical BVMD, other patients were multifocal vitelliform macular dystrophy. The DNA sequencing result showed that all the 4 patients carried heterozygous missense mutations in exon 3 of BEST1 gene: c.240C>G (p.F80L) (M1) and 2 members carried this mutation, but without clinical phenotype. M1 was a likely-pathogenic mutation reported for the first time. In family 2, the proband and the other patient were diagnosed as ARB. The DNA result showed that the 2 patients carried heterozygous missense mutations in exon 5 and exon 2 of BEST1 gene: c.584C>T (p.A195V) (M2)、c.139C>A (p.R47S) (M3), and a heterozygous frameshift mutation in exon 3 of BEST1 gene: c.235dupT (p.S79Ffs*153) (M4). M2 was a pathogenic mutation reported previously. M3 variant was of undetermined significance. M4 was a first reported pathogenic mutation. Conclusions:The BEST1 gene mutation is the main cause of BVMD and ARB. Different mutation sites have different clinical phenotypes. BVMD and ARB have genetic and clinical heterogeneity.
