Dominant optic atrophy: correlation between clinical and molecular genetic studies.
OBJECTIVE
To assess the clinical picture and molecular genetics of 14 Finnish families with dominant optic atrophy (DOA).


METHODS
The clinical status of family members was based on the assessment of visual acuity, colour vision, visual fields and optic nerve appearance; 31 individuals were affected, two suspect and 21 unaffected. A total of 30 coding exons and exon- intron boundaries of the OPA1 gene were sequenced in order to detect mutations.


RESULTS
Half the patients were diagnosed at the age of < or = 20 years. Ten out of 20 affected individuals followed up for > or = 6 years had a progressive disease and 10 had a stable disease. According to WHO criteria, 36% of the affected patients were visually handicapped. Eight OPA1 pathogenic mutations, all but one novel, and 18 neutral polymorphisms were detected.


CONCLUSIONS
The most sensitive indicators of DOA were optic disc pallor and dyschromatopsia. With molecular genetic analysis, asymptomatic mutation carriers and DOA cases with a mild clinical outcome were ascertained. No mutational hotspot or Finnish major mutation in the OPA1 gene could be demonstrated as most families carried a unique mutation. No obvious genotype- phenotype correlation could be detected. Detailed clinical assessment and exclusion of non-DOA families prior to mutation screening are necessary for obtaining a high mutation detection rate.
Puomila
Anu
A
Department of Medical Genetics, University of Turku, Turku, Finland. anu.puomila@utu.fi
Huoponen
Kirsi
K
Mäntyjärvi
Maija
M
Hämäläinen
Petra
P
Paananen
Reetta
R
Sankila
Eeva-Marja
EM
Savontaus
Marja-Liisa
ML
Somer
Mirja
M
Nikoskelainen
Eeva
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003117:Color Vision Defects / Q000175:diagnosis; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000175:diagnosis* / Q000235:genetics*; D009898:Optic Disk / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014792:Visual Acuity; D014794:Visual Fields
D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human