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Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations


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Cohn, AC, Toomes, C, Potter, C, Towns, KV, Hewitt, AW, Inglehearn, CF, Craig, JE and Mackey, DA 2007 , 'Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations' , American Journal of Ophthalmology, vol. 143, no. 4 , pp. 656-662 , doi: 10.1016/j.ajo.2006.12.038.

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PURPOSE: We identified families with autosomal dominant
optic atrophy (ADOA), determined the number
and type of OPA1 mutations, and investigated the phenotypic
variation and penetrance in ADOA Australian
DESIGN: Cross-sectional genetics study.

METHODS: Probands were identified on the basis of
characteristic clinical features of ADOA. We screened
the OPA1 gene using single-strand conformational polymorphism,
heteroduplex analysis (SSCP/HA), or by
direct sequencing. Penetrance for pedigrees in which a
mutation of OPA1 had been identified was calculated
initially using all recruited individuals, and subanalysis
was performed using only those families for which there
was total recruitment of siblings.
RESULTS: A total of 406 patients from 17 pedigrees
were recruited, and OPA1 mutations were identified in
11/17 (65%) of these. The mean age at clinical examination
was 38.2 19.9 years (median age, 35 years;
range, four to 83 years). The median best-corrected
visual acuity in OPA1-mutation carriers was 20/70
(range, 20/16 to hand movements [HM]). The penetrance
in Australian ADOA pedigrees in the families
with complete sibling recruitment was 82.5%. On the
other hand, overall penetrance for all individuals harboring
an OPA1 mutation was 88%.
CONCLUSIONS: OPA1 mutations were identified in
11/17 (65%) of the ADOA pedigrees in this study. The
penetrance in our cohort was lower than originally
described (82.5% vs 98%) but higher than some recent
studies since the availability of genotyping. It is anticipated
that this figure would be even lower as more
asymptomatic individuals are identified. There are likely
to be other genetic and environmental modifiers influencing
disease penetrance.

Item Type: Article
Authors/Creators:Cohn, AC and Toomes, C and Potter, C and Towns, KV and Hewitt, AW and Inglehearn, CF and Craig, JE and Mackey, DA
Journal or Publication Title: American Journal of Ophthalmology
ISSN: 0002-9394
DOI / ID Number: 10.1016/j.ajo.2006.12.038
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