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OPA1 analysis in an international series of probands with bilateral optic atrophy
Author(s) -
Liskova P.,
Tesarova M.,
Dudakova L.,
Stepanka S.,
Kolarova H.,
Honzik T.,
Seto S.,
Votruba M.
Publication year - 2016
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2016.0358
Subject(s) - proband , haploinsufficiency , atrophy , genetics , medicine , pathology , mutation , biology , gene , phenotype
Purpose To determine the molecular genetic cause in previously unreported probands with optic atrophy from the United Kingdom, Czech Republic and Canada. Methods OPA1 coding regions and flanking intronic sequences were screened by direct sequencing in 44 probands referred with a diagnosis of bilateral optic atrophy. Detected rare variants were assessed for pathogenicity by in silico analysis. Segregation of the identified variants was performed in available first degree relatives. Results A total of 29 heterozygous mutations evaluated as pathogenic were identified in 42 probands, of these 7 were novel. In two probands only variants of unknown significance were found. 76% of pathogenic mutations observed in 30 (71%) out of 42 probands were evaluated to lead to unstable transcripts resulting in haploinsufficiency. Three probands with the following disease‐causing mutations c.1230 + 1G>A,c.1367G>A and c.2965dup were documented to suffer from hearing loss and/or neurological impairment. Conclusions OPA1 gene screening in patients with bilateral optic atrophy is an important part of clinical evaluation as it may establish correct clinical diagnosis. Our study expands the spectrum of OPA1 mutations causing dominant optic atrophy and supports the fact that haploinsufficiency is the most common disease mechanism.