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

May Sanyoura, Cédric Woudstra, George Halaby, Patrick Baz, Valérie Senée, Pierre Jean Guillausseau, Pierre Zalloua, Cécile Julier

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageBritish English
Pages (from-to)140-143
Number of pages4
JournalEuropean Journal of Human Genetics
Volume22
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Alström syndrome
  • diabetes
  • genetic diagnosis
  • monogenic disease
  • Wolfram syndrome

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