A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient

Eur J Hum Genet. 2014 Jan;22(1):140-3. doi: 10.1038/ejhg.2013.87. Epub 2013 May 8.


Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron-exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Alstrom Syndrome / genetics*
  • Alstrom Syndrome / pathology
  • Cell Cycle Proteins
  • Diabetes Insipidus, Neurogenic / complications
  • Diabetes Insipidus, Neurogenic / genetics
  • Diabetes Insipidus, Neurogenic / pathology
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / genetics
  • Diabetic Retinopathy / pathology
  • Genetic Linkage
  • Humans
  • Insulin Resistance / genetics
  • Ketosis / complications
  • Ketosis / genetics
  • Ketosis / pathology
  • Male
  • Mutation
  • Obesity / complications
  • Obesity / genetics
  • Obesity / pathology
  • Protein Isoforms / genetics*
  • Protein Isoforms / isolation & purification
  • Proteins / genetics*


  • ALMS1 protein, human
  • Cell Cycle Proteins
  • Protein Isoforms
  • Proteins