title: Alstrom syndrome (OMIM 203800): a case report and literature review.
abstract: BACKGROUND
  Alstrom syndrome (AS) is a rare autosomal recessive disease characterized by multiorgan dysfunction. The key features are childhood obesity, blindness due to congenital retinal dystrophy, and sensorineural hearing loss. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes, and hypertriglyceridemia. Thus, AS shares several features with the common metabolic syndrome, namely obesity, hyperinsulinemia, and hypertriglyceridemia. Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.
  
  
  METHODS
  We describe the case of a 27-year old female from an English (Caucasian) kindred. She had been initially referred for hypertriglyceridemia, but demonstrated other features suggestive of AS, including blindness, obesity, type 2 diabetes, renal dysfunction, and hypertension. DNA analysis revealed that she is a compound heterozygote with two novel mutations in the ALMS1 gene - H3882Y and V424I. Examination of her family revealed that her phenotypically unaffected mother and younger sister also had heterozygous mutations in the ALMS1 gene. In addition to presenting these novel molecular findings for AS, we review the clinical and genetic features of AS in the context of our case.
  
  
  CONCLUSIONS
  Two novel mutations in the ALMS1 gene causative for AS have been reported here, thereby increasing the number of reported mutations to 81 and providing a wider basis for mutational screening among affected individuals.
authors.affiliation: Department of Vascular Biology and Medicine, Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. tjoy@uwo.ca
authors.forename: Tisha
authors.initials: T
authors.lastname: Joy
authors.forename: Henian
authors.initials: H
authors.lastname: Cao
authors.forename: Graeme
authors.initials: G
authors.lastname: Black
authors.forename: Rayaz
authors.initials: R
authors.lastname: Malik
authors.forename: Valentine
authors.initials: V
authors.lastname: Charlton-Menys
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Paul N
authors.initials: PN
authors.lastname: Durrington
mesh_terms: D000328:Adult; D001766:Blindness / Q000235:genetics*; D018797:Cell Cycle Proteins; D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000235:genetics*; D006973:Hypertension / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009765:Obesity; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins