ALMS1 Protein-Associated Cardiomyopathy

Abstract

Alström syndrome is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene. ALMS1, located on chromosome 2p13, encodes for a large protein of length 4,169 amino acids. The biological role of ALM1 has been implicated in the function of primary cilia and intracellular trafficking. Mutations in ALMS1 are often nonsense or frameshift mutations and primarily affect exons 8, 10, and 16 of the gene. Alström syndrome, a rare monogenic form of ciliopathy, is characterized by early onset childhood obesity, dilated cardiomyopathy (DCM), bilateral sensorineural hearing loss (SNHL), type 2 diabetes mellitus (T2D), and insulin resistance. With over 1,200 cases of Alström syndrome reported globally, ALMS1 is a rapidly growing area of interest. This Honors in the Major thesis seeks to use Drosophila melanogaster as a model organism for demonstrating how ALMS1 mutation affects the heart and can lead to the development of cardiomyopathy. Further, much is still unknown about ALMS1 structure and function. Alström syndrome can differ in severity, making a diagnosis difficult. This thesis aims to highlight current clinical findings involving ALMS1 and Alström syndrome presentation. By better understanding ALMS1, early genetic screening, diagnosis, and management of Alström syndrome can be obtained.