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Detection of a novel premature stop codon in the OPA1 gene in autosomal dominant optic atrophy
Author(s) -
OLDAK M,
FEDEROWICZ A,
SZULBORSKI K,
WIERZBOWSKA J,
KOSINSKA J,
PIOSKI R,
SZAFLIK JP,
SZAFLIK J
Publication year - 2012
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.1755-3768.2012.2785.x
Subject(s) - genetics , genetic linkage , exon , locus (genetics) , stop codon , biology , gene , atrophy
Purpose Autosomal dominant optic atrophy (ADOA) is a genetically heterogeneous disease, with OPA1, OPA4, and OPA5 representing the main ADOA loci. The aim of the study was to identify genetic etiology of inherited optic neuropathy in a Polish family. Methods We report on a 2‐generation Polish family with ADOA in which nine family members are affected. MRI and detailed ophthalmological examination with visual field and electrophysiological testing were performed. DNA was obtained from blood samples and linkage to known ADOA loci as well as sequencing of 29 OPA1 exons were conducted. Amplified fragments were analyzed on an automatic DNA sequencer. Results MRI and ophthalmological examination confirmed the diagnosis of bilateral optic neuropathy. Pattern visual evoked potentials (PVEP) presented delayed P100 wave latency, reduced N75/P100 amplitude and abnormal morphology of waves. Pedigree analysis demonstrated a dominant mode of inheritance. Linkage studies allowed the exclusion of OPA4 and OPA5 loci but revealed linkage to the major OPA1 locus in the investigated family. Sequencing of the OPA1 gene identified a novel C‐to‐T transiton in exon 2 prediciting a premature stop codon (Q31X). The mutation co‐segratated with the phenotype in this family. No other alteration was found in the OPA1 gene. Conclusion Occurrence of the premature termination codon at the beginning of the transcript strongly suggest that ADOA in the investigated family is a consequence of OPA1 haploinsufficiency. The novel variant broadens the spectrum of the reported OPA1 mutations causing ADOA.