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Alström Syndrome: Mutation Spectrum of ALMS1
Author(s) -
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.
Publication year - 2015
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22796
Subject(s) - ciliopathy , biology , genetics , mutation , bioinformatics , gene , phenotype
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.