Clinical and genetic analysis of a Chinese patient with Alstr?m syndrome
10.3760/cma.j.cn511374-20230401-00184
- VernacularTitle:Alstr?m综合征1例患者的临床与基因变异分析
- Author:
Jiayue LI
1
;
Jie GAO
;
Lin WANG
;
Yanhua LI
;
Ming ZHANG
;
Xietian PAN
;
Xinhong GUO
Author Information
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
- Keywords:
Alstr?m syndrome;
ALMS1 gene;
Dilated cardiomyopathy
- From:
Chinese Journal of Medical Genetics
2024;41(5):596-600
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology for a patient with Alstr?m 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.
