Premium
OPA 1 analysis in an international series of probands with bilateral optic atrophy
Author(s) -
Liskova Petra,
Tesarova Marketa,
Dudakova Lubica,
Svecova Stepanka,
Kolarova Hana,
Honzik Tomas,
Seto Sharon,
Votruba Marcela
Publication year - 2017
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/aos.13285
Subject(s) - proband , haploinsufficiency , atrophy , genetics , medicine , mutation , pathology , 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 OPA 1 coding regions and flanking intronic sequences were screened by direct sequencing in 82 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 seven were novel. In two probands, only variants of unknown significance were found. 76% of pathogenic mutations observed in 30 (71%) 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 OPA 1 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 OPA 1 mutations causing dominant optic atrophy and supports the fact that haploinsufficiency is the most common disease mechanism.