Alström Syndrome: Mutation Spectrum of ALMS1

• Published in: Human mutation Vol. 36; no. 7; pp. 660 - 668
• Main Authors: Marshall, Jan D., Muller, Jean, Collin, Gayle B., Milan, Gabriella, Kingsmore, Stephen F., Dinwiddie, Darrell, Farrow, Emily G., Miller, Neil A., Favaretto, Francesca, Maffei, Pietro, Dollfus, Hélène, Vettor, Roberto, Naggert, Jürgen K.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-07-2015; Hindawi Limited
• Subjects: Adolescent; Adult; ALMS1; Alstrom Syndrome - genetics; Alström Syndrome; Cell Cycle Proteins; Child; ciliopathy; Exons; Genetic disorders; Humans; Mutation; Pedigree; Proteins - genetics; SNV; Young Adult; Alström Syndrome; SNV; ALMS1; ciliopathy
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.22796

ABSTRACT
Alström Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multisystem involvement including early cone‐rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of ALMS. Mutational analysis in a world‐wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with ALMS, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all ALMS1 mutations identified to date.
Alström Syndrome is a rare (<1/1,000,000) genetic disorder affecting multiple organ systems. In this report, we expand the spectrum of mutations of ALMS1 by mutational analysis in a world‐wide cohort of 204 families. We identified 109 novel mutations. We also provide an overview of the 240 known ALMS1 mutations identified to date and highlighting the allelic heterogeneity of this disorder. Additionally, we analyzed next generation sequencing data from 275 patients for rare or frequent Single Nucleotide Variants (SNVs).