Current Genomics

Christian Néri
Institute of Biology Paris-Seine
CNRS UMR 8256 and UPMC
Paris, 75005
France

Back

Alstrom Syndrome: Genetics and Clinical Overview

Author(s): Jan D. Marshall, Pietro Maffei, Gayle B. Collin, Jurgen K. Naggert.

Abstract:

Alstrom syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background.

Alstrom syndrome is caused by mutations in ALMS1, a large gene comprised of 23 exons and coding for a protein of 4,169 amino acids. In general, ALMS1 gene defects include insertions, deletions, and nonsense mutations leading to protein truncations and found primarily in exons 8, 10 and 16. Multiple alternate splice forms exist. ALMS1 protein is found in centrosomes, basal bodies, and cytosol of all tissues affected by the disease. The identification of ALMS1 as a ciliary protein explains the range of observed phenotypes and their similarity to those of other ciliopathies such as Bardet- Biedl syndrome.

Studies involving murine and cellular models of Alström syndrome have provided insight into the pathogenic mechanisms underlying obesity and type 2 diabetes, and other clinical problems. Ultimately, research into the pathogenesis of Alstrom syndrome should lead to better management and treatments for individuals, and have potentially important ramifications for other rare ciliopathies, as well as more common causes of obesity and diabetes, and other conditions common in the general population.

Keywords: ALMS1, Alstrom syndrome, ciliopathy, truncal obesity, insulin resistance, hyperinsulinemia, cone-rod dystrophy, type 2 diabetes, hypertriglyceridemia, cardiomyopathy

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 12
ISSUE: 3
Year: 2011
Page: [225 - 235]
Pages: 11
DOI: 10.2174/138920211795677912
Price: $58