Alström综合征一个家系的临床特征与遗传学分析

Clinical characteristics and genetic analysis of a family with Alström syndrome

目的探讨1个Alström综合征家系的临床特征与遗传学病因。方法选取2021年2月于郑州大学第一附属医院就诊的1个Alström综合征家系(共5个成员)为研究对象。采集本研究Alström综合征家系的临床资料,抽取各成员的外周静脉血样,提取基因组DNA。应用全外显子组测序(WES)对大女儿与三儿子进行基因检测,应用Sanger测序进行家系验证,对候选变异进行致病性分析。结果大女儿(14岁)与三儿子(11岁)均患有先天性眼球震颤与弱视、发育迟缓及2型糖尿病。WES检测发现大女儿与三儿子均携带ALMS1基因c.3538A>T(p.Lys1180*)纯合变异,Sanger测序证实父亲、母亲与二女儿均携带ALMS1基因c.3538A>T(p.Lys1180*)杂合变异。根据《遗传变异分类标准与指南》与《原发性拷贝数变异解读与报告技术标准》,该变异被评定为致病性变异(PVS1+PM2_Supporting+PP4)结论ALSM1基因c.3538A>T(p.Lys1180*)纯合变异可能是本研究Alström综合征家系中大女儿与三儿子的遗传学致病原因,为其治疗提供参考依据。

ObjectiveTo explore the clinical characteristics and genetic etiology of a Chinese pedigree affected with Alström syndrome.MethodsA pedigree with 5 members affected with Alström syndrome who had visited the First Affiliated Hospital of Zhengzhou University in February 2021 was selected as the study subject.Clinical data of the pedigree were collected,and peripheral venous blood samples were collected for the extraction of genomic DNA.Genetic testing was carried out for the eldest daughter and third son through whole exome sequencing(WES).Candidate variant was verified by Sanger sequencing and bioinformatic analysis.ResultsThe eldest daughter(14 years old)and the third son(11 years old)both had congenital nystagmus,amblyopia,growth retardation and type 2 diabetes.WES revealed that both had harbored homozygous c.3538A>T(p.Lys1180*)variant of the ALMS1 gene.Sanger sequencing confirmed that the father,mother,and second daughter were all heterozygous carriers.Based on the Guidelines for Genetic Variation and the Technical Standards for Interpretation and Reporting of Primary Copy Number Variations,the variant was predicted as pathogenic(PVS1+PM2_Supporting+PP4).ConclusionThe homozygous c.3538A>T(p.Lys1180*)variant of the ALSM1 gene probably underlay the Alström syndrome in this pedigree,which has provided a reference for the clinical treatment.