Novel Mutations of the ALMS1 Gene in Patients with Alstrom Syndrome

Objective Alstrom syndrome is an autosomal recessive genetic disease caused by a mutation in the ALMS1 gene. Alstrom syndrome is clinically characterized by multisystem involvement, including sensorineural deafness, cone-rod dystrophy, nystagmus, obesity, insulin resistance, type 2 diabetes and hypogonadism. The diagnosis is thus challenging for patients without this characteristic set of clinical symptoms. We explored the effectiveness of whole-exome sequencing in the diagnosis of Alstrom syndrome. Methods A girl with symptoms of Alstrom syndrome was tested and diagnosed with the disease by wholeexome sequencing. Results Whole-exome sequencing revealed two novel variants, c.6160_6161insAT: p.Lys2054Asnfs*21(exon 8) and c.10823_10824 delAG:p.Glu 3608Alafs*9 (exon16) in the ALMS1 gene, leading to premature termination codons and the domain of ALMS1 protein. Blood sample testing of her asymptomatic parents revealed them to be heterozygous carriers of the same mutations. Assembly showed that the mutations on both alleles were located in conserved sequences. A review of the ALMS1 gene nonsense mutation status was performed. Conclusion We herein report two novel variants of the ALMS1 gene discovered in a Chinese Alstrom syndrome patient that expand the mutational spectrum of ALMS1 and provided new insight into the molecular mechanism underlying Alstrom syndrome. Our findings add to the current knowledge concerning the diagnosis and treatment of Alstrom syndrome.

Automated summary

Alstrom syndrome is a genetic disease caused by a mutation in the ALMS1 gene, characterized by multisystem involvement. Whole-exome sequencing plays an important role in diagnosing this disease. This study discovered two novel variants of the ALMS1 gene, expanding the understanding of Alstrom syndrome.