摘要
目的分析一个Alport综合征家庭的临床特征及遗传学病因。方法选取2019年12月于南通大学附属医院耳鼻咽喉科门诊就诊的一个AS耳聋家庭(NT103),该家庭家系成员包括父母姐妹4例,其中姐姐为AS患者(Ⅱ-1),其余人临床表现均无异常。对Alport综合征家庭进行详尽临床资料的收集和评估;采用基于家庭为单位,结合定向捕获技术二代测序的策略分析测序结果;对可疑致病基因的变异位点进行家庭内Sanger测序验证,依据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)指南确定变异致病性。结果该Alport综合征家庭的先证者表现为持续性血尿伴感音神经性聋但无眼部异常。定向捕获及Sanger测序显示,患者(Ⅱ-1)携带COL4A3复合杂合错义突变,c.4793T>G,p.L1598R/c.4981C>T,p.R1661C分别来自父母双亲,且在家系其他成员中共分离。根据ACMG指南,该Alport综合征家庭先证者携带的COL4A3基因复合杂合突变位点,判定为疑似致病变异。结论本研究丰富了COL4A3临床表型谱及基因突变谱。此外,对于疑似Alport综合征的患者,提倡常规开展基因检测以实现Alport综合征患者的早期个体化精准诊治。
Objective To report clinical characteristics and causative variants in a Chinese family with Alport syndrome(AS).Methods Data of members from a family with AS who visited the Otorhinolaryngology Clinic of Nantong University Affiliated Hospital in December 2019,including the parents and two sisters,were collected.One of the sisters was diagnosed with AS(II-1),while the rest of the family members showed no abnormal clinical manifestations.Family-based genetic analysis and targeted next-generation sequencing(NGS)for deafness-related genes were performed in the proband,and the results were verified by Sanger sequencing,followed by co-segregation analysis in all family members.Pathogenicity of variations was interpreted in accordance with the American College of Medical Genetics(ACMG)guidelines.Results The proband exhibited persistent hematuria and sensorineural hearing loss without ocular abnormalities.Compound heterozygous mutations in COL4A3 were identified in the proband,including c.4793T>G,p.L1598R,which was inherited from her father,and c.4981C>T,p.R1661C inherited from her mother.The bi-allelic mutations segregated in other family members were likely pathogenic in this family with autosomal recessive Alport syndrome(ARAS),according to the ACMG guidelines.Conclusion Our results expand the COL4A3 mutation spectrum and phenotypic spectrum of ARAS.In addition,family-based genetic testing should be considered in routine diagnosis of patients suspected as having ARAS.
作者
王雪纯
征丹娅
吕雪岩
唐艳
吴笛
陆赛男
张鲁平
WANG Xuechun;ZHENG Danya;LV Xueyan;TANG Yan;WU Di;LU Sainan;ZHANG Luping(Department of Otolaryngology-Head and Neck Surgery,Affiliated Hospital of Nantong University,Nantong University School of Medicine,Nantong 226001,China)
出处
《中华耳科学杂志》
CSCD
北大核心
2024年第4期579-582,共4页
Chinese Journal of Otology
基金
江苏省重点研发计划社会发展项目(BE2022764)。
