Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.

Human Molecular Genetics
Emily I SchindlerEdwin M Stone

Abstract

Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P < 10(-3)) and visual field (P < 10(-7)). Discordance between visual acuity and visual field in individual patients suggests the existence of at least two non-ABCA4 modifying factors. The findings of this study will facilitate the discovery of factors that modify ABCA4 disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.

References

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Citations

May 23, 2013·European Journal of Human Genetics : EJHG·Laura HeathfieldRajkumar S Ramesar
May 20, 2011·The New England Journal of Medicine·Val C Sheffield, Edwin M Stone
Aug 7, 2013·Human Molecular Genetics·Terry A BraunEdwin M Stone
Jan 25, 2014·The British Journal of Ophthalmology·Virginia Miraldi UtzElias I Traboulsi
Jun 19, 2013·Ophthalmology·Kaoru FujinamiAndrew R Webster
Jul 26, 2013·Ophthalmic Surgery, Lasers & Imaging Retina·Joshua CohenChristine N Kay
Feb 21, 2013·Ophthalmic Genetics·Kimiko SutoYoshihiro Hotta
Jul 25, 2015·Advances in Pediatrics·Alina V Dumitrescu, Arlene V Drack
Aug 21, 2013·American Journal of Ophthalmology·Kaoru FujinamiAndrew R Webster
Mar 4, 2014·European Journal of Ophthalmology·Chiara M EandiCristiana Marchese
Mar 2, 2017·Retina·Michael A KlufasSteven D Schwartz
Sep 6, 2012·Molecular Medicine Reports·Junhui YiQingjiong Zhang
Jan 1, 2021·Progress in Retinal and Eye Research·Andrew P VoigtRobert F Mullins
Mar 4, 2021·Current Opinion in Ophthalmology·Aaron M RiccaElliott H Sohn
Aug 28, 2021·Genes·Saoud Al-KhuzaeiStephanie Halford

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