Whole exome sequencing identified two homozygous ALMS1 mutations in an Iranian family with Alström syndrome.

Alström syndrome (AS) is a rare monogenic multi-system ciliopathy disorder with cardinal features, including cone-rod dystrophy, sensory neural hearing loss, metabolic dysfunctions and multiple organ failure caused by bi-allelic mutations in a centrosomal basal body protein-coding gene known as ALMS1. This study aimed to identify pathogenic mutations in a consanguineous Iranian family with AS. Next-generation sequencing was performed on the genomic DNA obtained from a 12 years old girl with AS. According to the bioinformatics analysis, computational modelling and segregation of variants, we identified two homozygous mutations close together in exon 8 of ALMS1 in the patient, including c.7262 G > T and c.7303-7305delAG. The clinically normal parents were heterozygous for both mutations. These mutations have a very rare frequency and only reported in the heterozygous state in the public genomic databases. Overall, due to the large size of the ALMS1 gene and clinical similarity with other ciliopathies and genetic disorders, whole exome sequencing can be useful for the identification of pathogenic mutations and the improvement of AS clinical management.