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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm
Human Molecular Genetics, Volume 22, No. 16, Article ddt179, Year 2013
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Description
The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease.Weused homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes.We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems. © The Author 2013. Published by Oxford University Press. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3723310/bin/supp_22_16_3250__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3723310/bin/supp_ddt179_ddt179supp.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3723310/bin/supp_ddt179_ddt179supp_fig1.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3723310/bin/supp_ddt179_ddt179supp_fig2.tif
Authors & Co-Authors
Yahyavi, Mani
United States, San Francisco
Division of Medical Genetics
Abouzeid, Hana
Switzerland, Lausanne
Université de Lausanne Unil
Gawdat, Ghada I.
Egypt, Giza
Cairo University
de Preux, Anne Sophie
United States, San Francisco
University of California, San Francisco
Xiao, Tong
United States, San Francisco
University of California, San Francisco
Bardakjian, Tanya
United States, Philadelphia
Albert Einstein Healthcare Network
Schneider, Adele S.
United States, Philadelphia
Albert Einstein Healthcare Network
Choi, Alex
United States, San Francisco
Division of Medical Genetics
Jorgenson, Eric M.
United States, Oakland
Kaiser Permanente Division of Research
Baier, Herwig
United States, San Francisco
University of California, San Francisco
Sada, Mohamad El
Egypt, Giza
Cairo University
Schorderet, Daniel F F.
Switzerland, Lausanne
École Polytechnique Fédérale de Lausanne
Switzerland, Sion
Institut de Recherche en Ophtalmologie
Switzerland, Sion
Iro
Slavotinek, Anne M.
United States, San Francisco
Division of Medical Genetics
Statistics
Citations: 67
Authors: 13
Affiliations: 9
Identifiers
Doi:
10.1093/hmg/ddt179
ISSN:
09646906
e-ISSN:
14602083
Research Areas
Genetics And Genomics
Health System And Policy