Analysis of USH2A gene mutation and clinical phenotype in families with Usher syndrome type 2 and retinitis pigmentosa
10.3760/cma.j.cn511434-20190912-00286
- VernacularTitle:2型Usher综合征和视网膜色素变性家系USH2A基因突变及临床表型分析
- Author:
Xiaomeng SHI
1
;
Ya LI
;
Kunpeng XIE
;
Ya YOU
;
Bo LEI
Author Information
1. 河南省人民医院 郑州大学人民医院 河南省眼科研究所 河南省立眼科医院 河南省眼科疾病临床医学研究中心，郑州 450003
- From:
Chinese Journal of Ocular Fundus Diseases
2020;36(3):178-183
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the gene mutations and clinical phenotypes in patients with Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP).Methods:From August 2018 to January 2019, 4 patients and 11 normal family members from 3 families of USH2 and RP who visited Henan Eye Hospital were enrolled in the study. Detailed medical history was obtained and visual acuity, fundus color photography, OCT, visual field, full field ERG examination were performed. Among the three families, pedigree 1 was diagnosed with USH2, pedigree 2 and pedigree 3 were diagnosed with RP. The peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. Targeted capture next generation sequencing analysis was performed on these members, and Sanger sequencing and family cosegregation were verified.Results:In the family F1, the proband had symptoms of RP and sensorineural deafness. Sequencing revealed two heterozygous frameshift variants: c.13877-13880 del AGAC (p. Q4626P) in exon 64 and c.798 del T (p. F266L) in exon 5 of USH2A. Both patients of family 2 and 3 showed RP signs without deafness. Two heterozygous variants c.15178T> C (p. S5060 P) in exon 70 and c.6986C> A (p. P2329H) in exon 37, and a pathogenic heterozygous variant c.5836C> T (p. R1946X) in exon 29 of USH2A were identified in family F2. A heterozygous missense variant c.14951C> T (p. P4984L) in exon 68 and a variant c.11156G> A (p. R3719H) in exon 57 of USH2A were found in family F3. The results of conservation analysis showed that the corresponding amino acid sites of USH2A p.Q4626P, p.F266L, p.S5060P, p.P2329H and p.P4984L were highly conserved in many species. Among these 7 pathogenic variants detected, M1-M4 and M6 were novel.Conclusions:Mutation USH2A gene are the main cause of USH2 and non-syndromic RP. Different variants affect protein translation and synthesis, consequently causing different clinical phenotypes.
