Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
目的：探讨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：选择2021年10月20日在解放军总医院第六医学中心就诊的41岁男性患者作为研究对象。进行了临床和实验室检查。全外显子组测序（WES）用于基因检测，和候选变异体通过Sanger测序和致病性分析进行验证。
结果：患者有以扩张型心肌病为特征的14年病史，完全性房室传导阻滞,视力障碍，感觉神经性听力损失,躯干肥胖，胰岛素抵抗，2型糖尿病,高血压,肾功能不全,和妄想症.基因检测显示，他携带了ALMS1基因的复合杂合变体，即c.6823C>T（p。Arg2275Ter）和c.9442_9445dup（p。Ser3149LysfsTer2）。桑格测序证实它们是从他的父亲和母亲那里继承的，分别。根据美国医学遗传学和基因组学学院（ACMG）的指南，两种变体均被预测为致病性的（PVS1_VeryStrongPM2_支持PM3PP3，PVS1_VeryStrongPM2_支持PM3）。文献回顾表明，患者的完全性房室传导阻滞是以前未报道的表型。
结论：c.6823C>T（p。Arg2275Ter）和c.9442_9445dup（p。Ser3149LysfsTer2）ALMS1基因的复合杂合变体可能是该患者的发病机理。以上发现扩展了ALMS的表型谱，并为处理类似病例的临床医生提供了见解。
方法：选择2021年10月20日在解放军总医院第六医学中心就诊的41岁男性患者作为研究对象。进行了临床和实验室检查。全外显子组测序（WES）用于基因检测，和候选变异体通过Sanger测序和致病性分析进行验证。
结果：患者有以扩张型心肌病为特征的14年病史，完全性房室传导阻滞,视力障碍，感觉神经性听力损失,躯干肥胖，胰岛素抵抗，2型糖尿病,高血压,肾功能不全,和妄想症.基因检测显示，他携带了ALMS1基因的复合杂合变体，即c.6823C>T（p。Arg2275Ter）和c.9442_9445dup（p。Ser3149LysfsTer2）。桑格测序证实它们是从他的父亲和母亲那里继承的，分别。根据美国医学遗传学和基因组学学院（ACMG）的指南，两种变体均被预测为致病性的（PVS1_VeryStrongPM2_支持PM3PP3，PVS1_VeryStrongPM2_支持PM3）。文献回顾表明，患者的完全性房室传导阻滞是以前未报道的表型。
结论：c.6823C>T（p。Arg2275Ter）和c.9442_9445dup（p。Ser3149LysfsTer2）ALMS1基因的复合杂合变体可能是该患者的发病机理。以上发现扩展了ALMS的表型谱，并为处理类似病例的临床医生提供了见解。
