title: Cataract as a phenotypic marker for a mutation in WFS1, the Wolfram syndrome gene.
abstract: OBJECTIVE
  Wolfram syndrome (WS) or diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) (OMIM 222300) is an inherited neurodegenerative disease characterized by diabetes mellitus and optic atrophy as the 2 major criteria, followed later in life by deafness, diabetes insipidus, and various signs of neurologic impairment. The presence of a cataract has been variably mentioned in WS.
  
  
  METHODS
  Two members of a family had thorough ophthalmic examination and their DNA was screened for mutations in mitochondrial DNA, WFS1, OPA1, and OPA3 genes.
  
  
  RESULTS
  We report a patient who first had surgery for bilateral cataract at age 5 and who subsequently presented typical signs of WS, i.e., diabetes mellitus, optic atrophy with reduced visual acuity at 20/400 on both eyes at age 22, and mild deafness. The patient was found to be a compound heterozygote for 2 truncating mutations in WFS1, the major WS gene. She carried the previously reported c.1231_1233 delCT and a novel c.2431_2465dup35 mutation. She also was heterozygote for a novel OPA1 sequence variant, c.929A>G in exon 9, whose pathogenicity remains uncertain. The patient's mother was a heterozygous carrier of the c.2431_2465dup35 mutation. She did not have diabetes mellitus or optic atrophy but had bilateral polar cataract. She did not carry the OPA1 sequence variant.
  
  
  CONCLUSIONS
  Cataract could be a marker for the WFS1 heterozygosity in this family, namely the c.2431_2465dup35 mutation.
authors.affiliation: CHRU Montpellier, Centre de Référence Genetic Sensory Diseases, Montpellier, France.
authors.forename: Salah Mohamed Cherif
authors.initials: SM
authors.lastname: Titah
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.forename: Catherine
authors.initials: C
authors.lastname: Blanchet
authors.forename: Severine
authors.initials: S
authors.lastname: Lopez
authors.forename: Gerard
authors.initials: G
authors.lastname: Rondouin
authors.forename: Guy
authors.initials: G
authors.lastname: Lenaers
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.forename: Veronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000328:Adult; D002386:Cataract / Q000175:diagnosis / Q000235:genetics*; D002387:Cataract Extraction; D004272:DNA, Mitochondrial / Q000235:genetics; D005074:Evoked Potentials, Visual / Q000502:physiology; D005091:Exons / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D014929:Wolfram Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers; D008565:Membrane Proteins; C443108:OPA3 protein, human; D011506:Proteins; C114987:wolframin protein; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human