Alström综合征1例患者的临床与基因变异分析  

Clinical and genetic analysis of a Chinese patient with Alström syndrome

作　　者：李佳月 高洁 王琳 李彦华 章明 潘谢添 郭新红 Li Jiayue;Gao Jie;Wang Lin;Li Yanhua;Zhang Ming;Pan Xietian;Guo Xinhong(Department of Cardiovascular Medicine,the Sixth Medical Center,PLA General Hospital,Beijing 100853,China;Department of Cardiology,Hebei General Hospital,Shijiazhuang,Hebei 050051,China)

机构地区：[1]中国人民解放军总医院第六医学中心心血管病医学部,北京100853 [2]河北省总医院心内科,石家庄050051

出　　处：《中华医学遗传学杂志》2024年第5期596-600,共5页Chinese Journal of Medical Genetics

摘　　要：目的分析1例表现为扩张型心肌病的Alström综合征(ALMS)患者的遗传学病因。方法选取2021年10月20日就诊于中国人民解放军总医院心血管病医学部的1例41岁男性ALMS患者作为研究对象,对其进行临床和实验室检查,应用全外显子组测序技术进行检测,对候选变异进行Sanger测序验证和致病性分析。结果患者病史14年,表现为扩张型心肌病、完全性房室传导阻滞、视力受损、感音神经性听力损失、躯干型肥胖、胰岛素抵抗、2型糖尿病、高血压、肾功能不全以及被迫害妄想症。基因检测提示其携带ALMS1基因c.6823C>T(p.Arg2275Ter)和c.9442_9445dup(p.Ser3149LysfsTer2)复合杂合变异,经Sanger测序验证分别遗传自其父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南,上述变异均被判定为致病性(PVS1_VeryStrong+PM2_Supporting+PM3+PP3;PVS1_VeryStrong+PM2_Supporting+PM3)。文献回顾提示,患者的完全性房室传导阻滞为既往未见报道的表型。结论ALMS1基因c.6823C>T(p.Arg2275Ter)和c.9442_9445dup(p.Ser3149LysfsTer2)复合杂合变异可能是上述患者的遗传学病因。上述发现丰富了ALMS的临床表型谱,为患者的临床诊断提供了依据。Objective To explore the genetic etiology for a patient with Alström syndrome(ALMS)presenting as dilated cardiomyopathy.Methods A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20,2021 was selected as the study subject.Clinical and laboratory examinations were carried out.Whole exome sequencing(WES)was employed for genetic testing,and candidate variants were validated by Sanger sequencing and pathogenicity analysis.Results The patient had a 14-year medical history characterized by dilated cardiomyopathy,complete atrioventricular block,visual impairment,sensorineural hearing loss,truncal obesity,insulin resistance,type 2 diabetes,hypertension,renal dysfunction,and paranoid delusions.Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene,namely c.6823C>T(p.Arg2275Ter)and c.9442_9445dup(p.Ser3149LysfsTer2).Sanger sequencing confirmed that they were inherited from his father and mother,respectively.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were predicted to be pathogenic(PVS1_VeryStrong+PM2_Supporting+PM3+PP3,PVS1_VeryStrong+PM2_Supporting+PM3).Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously.Conclusion The c.6823C>T(p.Arg2275Ter)and c.9442_9445dup(p.Ser3149LysfsTer2)compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient.Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.

关 键 词：Alström综合征 ALMS1基因 扩张型心肌病 

分 类 号：R542.2[医药卫生—心血管疾病]