Usher综合征2型及视网膜色素变性家系USH2A基因突变及临床表型分析

Q4 Medicine

中华眼底病杂志 Pub Date : 2020-03-25 DOI:10.3760/CMA.J.CN511434-20190912-00286

Xiaomeng Shi, Ya Li, Kunpeng Xie, Y. You

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Targeted capture next generation sequencing analysis was performed on these members, and Sanger sequencing and family cosegregation were verified. \n \n \nResults \nIn 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. 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引用次数: 0

摘要

目的观察2型Usher综合征（USH2）和色素性视网膜炎（RP）患者的基因突变和临床表型。方法从2018年8月至2019年1月，河南省眼科医院就诊的USH2和RP 3个家庭的4名患者和11名正常家庭成员参加了研究。详细病史，进行视力、眼底彩色摄影、OCT、视野、全视野ERG检查。在这三个家族中，系谱1被诊断为USH2，系谱2和系谱3被诊断为RP。采集患者及其家族成员的外周静脉血，提取全基因组DNA。对这些成员进行了靶向捕获下一代测序分析，并验证了Sanger测序和家族共分离。结果在F1家系中，先证者有RP和感音神经性耳聋的症状。测序显示两个杂合移码变体：USH2A外显子64中的c.13877-13880 del AGAC（第Q4626P页）和外显子5中的c.798 del T（第F266L页）。家系2和家系3的患者均表现出RP体征，无耳聋。在F2家族中鉴定出USH2A外显子70中的两个杂合变体c.15178T>c（p.S5060 p）和外显子37中的c.6986C>A（p.P2329H），以及外显子29中的一个致病性杂合变体c.5836C>T（p.R1946X）。在F3家族中发现了USH2A外显子68中的杂合错义变体c.14951C>T（第P4984L页）和外显子57中的变体c.11156G>A（第R3719H页）。保存分析结果表明，USH2A p.Q4626P、p.F266L、p.S5060P、p.P2329H和p.P4984L的相应氨基酸位点在许多物种中高度保守。在检测到的7种致病性变体中，M1-M4和M6是新的。结论突变的USH2A基因是引起USH2和非综合征性RP的主要原因，不同的突变影响蛋白质的翻译和合成，从而导致不同的临床表型。关键词：亚瑟综合征；色素性视网膜炎；隐性基因；突变

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Analysis of USH2A gene mutation and clinical phenotype in families with Usher syndrome type 2 and retinitis pigmentosa

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. Key words: Usher syndromes; Retinitis pigmentosa; Genes, recessive; Mutation

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来源期刊

中华眼底病杂志 Medicine-Ophthalmology

CiteScore

0.40

自引率

0.00%

发文量

5383

期刊介绍： Chinese Journal of Ocular Fundus Diseases is the only scientific journal in my country that focuses on reporting fundus diseases. Its purpose is to combine clinical and basic research, and to give equal importance to improvement and popularization. It comprehensively reflects the leading clinical and basic research results of fundus disease disciplines in my country; cultivates professional talents in fundus disease, promotes the development of fundus disease disciplines in my country; and promotes academic exchanges on fundus disease at home and abroad. The coverage includes clinical and basic research results of posterior segment diseases such as retina, uveal tract, vitreous body, visual pathway, and internal eye diseases related to systemic diseases. The readers are medical workers and researchers related to clinical and basic research of fundus diseases. According to the journal retrieval report of the Chinese Institute of Scientific and Technological Information, the comprehensive ranking impact factor and total citation frequency of the Chinese Journal of Ocular Fundus Diseases have been among the best in the disciplines of ophthalmology, otolaryngology, and ophthalmology in my country for many years. The papers published have been included in many important databases at home and abroad, such as Scopus, Peking University Core, and China Science Citation Database (CSCD).