title: Neurologic features and genotype-phenotype correlation in Wolfram syndrome.
abstract: OBJECTIVE
  Wolfram syndrome (WS) is a rare neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and optic atrophy. Our aim was to describe the nature and the frequency of the neurologic manifestations, which had been poorly studied until now.
  
  
  METHODS
  We performed a detailed clinical study with genotype-phenotype correlation in a series of 59 patients with WS.
  
  
  RESULTS
  The onset of neurologic symptoms, with a median age of 15 years, was much earlier than previously reported. Cognitive impairment, which was not frequent in previous reports, was observed in 32% of patients with neurologic signs. Like epilepsy, it was mainly found in patients who developed neurologic signs before 15 years of age. In contrast to previous series, we also found malformations of cortical development on magnetic resonance imaging in epileptic children and white matter involvement, including diffuse leukoencephalopathy, in adult patients. We identified 109 mutated alleles corresponding to 56 different mutations of the WFS1 gene, among which 10 were novel. Homozygosity or compound heterozygosity for missense mutation does not seem to influence the age of onset and the occurrence of neurologic complications. However, an interesting point concerns a possible correlation between the location of the mutations and the development of the neurologic manifestations.
  
  
  CONCLUSIONS
  This series concerns the largest cohort of WS patients reported to date. It illustrates the wide variety of neurologic signs in this syndrome and the necessity of rapid therapeutic coverage to improve the prognosis.
authors: Department of Medical Genetics, Archet 2 Hospital, CHU of Nice, France.
authors: Annabelle
authors: A
authors: Chaussenot
authors: Sylvie
authors: S
authors: Bannwarth
authors: Cecile
authors: C
authors: Rouzier
authors: Bernard
authors: B
authors: Vialettes
authors: Samira Ait El
authors: SA
authors: Mkadem
authors: Brigitte
authors: B
authors: Chabrol
authors: Aline
authors: A
authors: Cano
authors: Pierre
authors: P
authors: Labauge
authors: Véronique
authors: V
authors: Paquis-Flucklinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D002648:Child; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics*; D004827:Epilepsy; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009422:Nervous System Diseases / Q000150:complications / Q000235:genetics*; D014929:Wolfram Syndrome / Q000150:complications / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein