title: Novel OPA1 missense mutation in a family with optic atrophy and severe widespread neurological disorder.
abstract: OBJECTIVE
  To identify the underlying molecular genetic cause in a Czech family with optic atrophy, deafness, ptosis, ophthalmoplegia, polyneuropathy and ataxia transmitted as an autosomal dominant trait.
  
  
  METHODS
  Ophthalmological and neurological examination followed by molecular genetic analyses.
  
  
  RESULTS
  Seven family members were clinically affected. There was a variable but progressive visual, hearing and neurological disability across the family as a whole. The majority of subjects presented with impairment of visual function and a variable degree of ptosis and/or ophthalmoplegia from the first to the third decade of life. Deafness, neuropathy and ataxia appeared later, in the third and fourth decade. Migraine, tachycardia, intention tremor, nystagmus and cervical dystonia were observed in isolated individuals. A significant overall feature was the high level of neurological disability leading to 3 of 4 members being unable to walk or stand unaided before the age of 60 years. A novel missense mutation c.1345A>C (p.Thr449Pro) in OPA1 segregating with the disease phenotype over three generations was detected. In silico analysis supported pathogenicity of the identified sequence variant.
  
  
  CONCLUSIONS
  Our work expands the spectrum of mutation in OPA1, which may lead to severe multisystem neurological disorder. The molecular genetic cause of dominant optic atrophy in the Czech population is reported for the first time. We propose that regular cardiac follow-up in patients diagnosed with dominant optic atrophy and widespread neurological disease should be considered.
authors: Laboratory of the Biology and Pathology of the Eye, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors: Petra
authors: P
authors: Liskova
authors: Olga
authors: O
authors: Ulmanova
authors: Petr
authors: P
authors: Tesina
authors: Hana
authors: H
authors: Melsova
authors: Pavel
authors: P
authors: Diblik
authors: Hana
authors: H
authors: Hansikova
authors: Marketa
authors: M
authors: Tesarova
authors: Marcela
authors: M
authors: Votruba
mesh_terms: D000328:Adult; D000368:Aged; D001763:Blepharoptosis / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005838:Genotype; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017246:Ophthalmoplegia, Chronic Progressive External / Q000175:diagnosis / Q000235:genetics*; D009896:Optic Atrophy / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D041623:Tomography, Optical Coherence
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human