Novel OPA1 missense mutation in a family with optic atrophy and severe widespread neurological disorder

0392766 - ÚOCHB 2014 RIV DK eng J - Journal Article
Lisková, P. - Ulmanová, O. - Těšina, Petr - Melsová, H. - Diblik, P. - Hansíková, H. - Tesařová, M. - Votruba, M.
Novel OPA1 missense mutation in a family with optic atrophy and severe widespread neurological disorder.
Acta Ophthalmologica. Roč. 91, č. 3 (2013), E225-E231. ISSN 1755-375X. E-ISSN 1755-3768
Grant - others:GA MZd(CZ) NT11190
Institutional research plan: CEZ:AV0Z40550506
Keywords : ataxia * autosomal dominant * deafness * encephalomyopathy
Subject RIV: FF - HEENT, Dentistry
Impact factor: 2.512, year: 2013

Purpose: 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. Conclusion: 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.
Permanent Link: http://hdl.handle.net/11104/0221562