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


Cohn, AC and Toomes, C and Potter, C and Towns, KV and Hewitt, AW and Inglehearn, CF and Craig, JE and Mackey, DA, Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations, American Journal of Ophthalmology, 143, (4) pp. 656-662. ISSN 0002-9394 (2007) [Refereed Article]

DOI: doi:10.1016/j.ajo.2006.12.038


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 pedigrees.

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 Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:50097
Year Published:2007
Web of Science® Times Cited:89
Deposited By:Medicine
Deposited On:2007-08-01
Last Modified:2014-10-06

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