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

Emily I Schindler; Erik L Nylen; Audrey C Ko; Louisa M Affatigato; Andrew C Heggen; Kai Wang; Val C Sheffield; Edwin M Stone

doi:10.1093/hmg/ddq284

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

Journal article

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Peer reviewed

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

Emily I Schindler, Erik L Nylen, Audrey C Ko, Louisa M Affatigato, Andrew C Heggen, Kai Wang, Val C Sheffield and Edwin M Stone

Human molecular genetics, Vol.19(19), pp.3693-3701

10/01/2010

DOI: 10.1093/hmg/ddq284

PMCID: PMC2935854

PMID: 20647261

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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.

Genetics, Population

Visual Fields - physiology

Genetic Association Studies

Genes, Recessive - genetics

Humans

Retinitis Pigmentosa - genetics

Regression Analysis

ATP-Binding Cassette Transporters - genetics

Time Factors

Alleles

Fundus Oculi

Retinitis Pigmentosa - physiopathology

Visual Acuity - physiology

Details

Title: Subtitle: Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population
Creators: Emily I Schindler - Howard Hughes Medical Institute, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA
Erik L Nylen
Audrey C Ko
Louisa M Affatigato
Andrew C Heggen
Kai Wang
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.19(19), pp.3693-3701
DOI: 10.1093/hmg/ddq284
PMID: 20647261
PMCID: PMC2935854
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Grant note: R01 EY016822 / NEI NIH HHS Howard Hughes Medical Institute R01 EY017168 / NEI NIH HHS
Language: English
Date published: 10/01/2010
Academic Unit: Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Biostatistics; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980050902771

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