Whole Exome Sequencing (WES) Identified ALMS1 Mutation in a Thai Boy with Alström syndrome-A First Report at Phramongkutklao Hospital

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Yutthana Pansuwan
Voraluck Phatarakijnirund
Boonchai Boonyawat
Tim Phetthong


Alström syndrome (ALMS) is a rare autosomal recessive multi-system disorder with a phenotypic variability and is characterized by cone-rod dystrophy, sensorineural hearing loss, obesity, insulin resistance/type 2 diabetes mellitus (T2DM), cardiomyopathy and progressive pulmonary, hepatic and renal dysfunction. ALMS is caused by mutations in the Alström syndrome protein 1 (ALMS1) gene. Herein, we report a 15-year-old Thai boy with ALMS presenting with childhood onset retinal degeneration, obesity with T2DM, hypertriglyceridemia and non-alcoholic steatohepatitis, sensorineural hearing loss and dilated cardiomyopathy (DCM). Whole exome sequencing (WES) of the patient’s genomic DNA identified two compound heterozygous mutations including one frameshift mutation; c.6166_6167dup or p.Leu2057PhefsTer17, in exon 8 and one nonsense mutation; c.10822C>T or p.Arg3608Ter, in exon 16 of ALMS1 gene. Both mutations were predicted to result in either absence or truncation of ALMS1 proteins. This report highlighted the clinical utility of WES as a powerful tool for diagnosis of genetic heterogeneity disorders and the rare diseases including ALMS. 

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นิพนธ์ต้นฉบับ (Original Article)


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