Alström Syndrome: Mutation Spectrum of ALMS1 |
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| Authors: | Jan D. Marshall Jean Muller Gayle B. Collin Gabriella Milan Stephen F. Kingsmore Darrell Dinwiddie Emily G. Farrow Neil A. Miller Francesca Favaretto Pietro Maffei Hélène Dollfus Roberto Vettor Jürgen K. Naggert |
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| Affiliation: | 1. The Jackson Laboratory, Bar Harbor, Maine;2. Alstr?m Syndrome International, Mount Desert, Maine;3. IGBMC, CNRS UMR 7104/INSERM U964/University of Strasbourg, Illkirch Cedex, France;4. Laboratoire ICUBE, UMR CNRS 7357, LBGI, Université de Strasbourg, Strasbourg, France;5. Laboratoire de Diagnostic Génétique, H?pitaux Universitaires de Strasbourg, Strasbourg Cedex, France;6. Department of Medicine, University of Padua, Padua, Italy;7. Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri;8. Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico;9. Laboratoire de Génétique médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine FMTS, Université de Strasbourg, Strasbourg, France;10. Service de Génétique Médicale, Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), H?pitaux Universitaires de Strasbourg, Strasbourg, France |
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| 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. |
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| Keywords: | ALMS1 Alströ m Syndrome ciliopathy SNV |
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