Mutations in ALDH1A3 cause microphthalmia

Authors

  • M A Aldahmesh,

    1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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  • A O Khan,

    1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
    2. Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
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  • H Hijazi,

    1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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  • F S Alkuraya

    Corresponding author
    1. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
    • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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  • Authors declare no conflict of interest.

Corresponding author: Fowzan S. Alkuraya, MD, Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia.

Tel.: +966 1 442 7875;

fax: +966 1 442 4585;

e-mail: falkuraya@kfshrc.edu.sa

Abstract

Microphthalmia is an important inborn error of eye development that can be associated with multisystem involvement. Anophthalmia is more severe and rarer. Single mutations in an expanding list of genes are known to cause this spectrum of anomaly. In one branch of a multiplex family with microphthalmia and anophthalmia, autozygome analysis excluded all known microphthalmia genes at the time of doing this study. Exome sequencing and autozygome filtration identified a novel homozygous variant in ALDH1A3. Subsequently, we identified another homozygous variant in 2 of the 10 probands with microphthalmia we specifically screened for mutations in ALDH1A3. Interestingly, the other branch of the original family was found to segregate anophthalmia/syndactyly with a novel homozygous SMOC1 variant. Our data support the very recent and independent identification of ALDH1A3 as a disease gene in microphthalmia. Locus heterogeneity should be considered in consanguineous families even for extremely rare phenotypes.

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