Diagnosing Alström syndrome in a patient followed up with syndromic obesity for years

• Published in: Intractable & Rare Diseases Research p. 2022.01024
• Main Authors: Yakubi, Mustafa, Cicek, Dilek, Demir, Mikail, Yildirim, Abdulbaki, Hatipoglu, Nihal, Ozkul, Yusuf, Dundar, Munis
• Format: Journal Article
• Language: English
• Published: International Research and Cooperation Association for Bio & Socio-Sciences Advancement 2022
• Subjects: ALMS1 gene; biallelic mutations; obesity; rare diseases
• ISSN: 2186-3644; 2186-361X
• DOI: 10.5582/irdr.2022.01024

Alström syndrome (AS) is a rare autosomal recessive monogenic disorder caused by mutations of the Alström syndrome 1 (ALMS1) gene, located on chromosome 2p13. It is a progressive multisystemic disease characterized mostly by obesity, sensorineural hearing loss, visual impairments, cardiomyopathy, insulin resistance and/or type 2 diabetes mellitus (T2DM), metabolic dysfunctions, non-alcoholic fatty liver disease, and chronic progressive kidney disease. Generally, the first clinical symptoms of the disease appear in the first years of life with a major variation of onset age. In this study, we aimed to examine the molecular diagnosis of a 6-year-old patient with suspected AS clinical symptoms. After applying clinical exome sequencing (CES) in the patient we found a homozygous deletion in exon 8 at the ALMS1 gene (c.2311_2312del). We identified a homozygous frameshift mutation. The reported variant was pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG). Thus, the patient was diagnosed with AS as a result of the combined clinical phenotype and genetic tests results. We hope the variant we found can expand the spectrum of ALMS1 variants in AS.