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Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with leber congenital amaurosis

Authors

  • Xia Wang,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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    • These two authors contributed equally to this work.

  • Hui Wang,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
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    • These two authors contributed equally to this work.

  • Ming Cao,

    1. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
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  • Zhe Li,

    1. Department of Bioengineering, University of California at San Diego, La Jolla, California
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  • Xianfeng Chen,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Claire Patenia,

    1. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
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  • Athurva Gore,

    1. Department of Bioengineering, University of California at San Diego, La Jolla, California
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  • Emad B. Abboud,

    1. King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
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  • Ali A. Al-Rajhi,

    1. King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
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  • Richard A. Lewis,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Ophthalmology, Baylor College of Medicine, Houston, Texas
    3. Texas Children's Hospital, Baylor College of Medicine, Houston, Texas
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  • James R. Lupski,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Texas Children's Hospital, Baylor College of Medicine, Houston, Texas
    3. Department of Neurology, Baylor College of Medicine, Houston, Texas
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  • Graeme Mardon,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Neurology, Baylor College of Medicine, Houston, Texas
    3. Department of Neuroscience, Baylor College of Medicine, Houston, Texas
    4. Department of Pathology, Baylor College of Medicine, Houston, Texas
    5. Program in Developmental Biology, Baylor College of Medicine, Houston, Texas
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  • Kun Zhang,

    1. Department of Bioengineering, University of California at San Diego, La Jolla, California
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  • Donna Muzny,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
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  • Richard A. Gibbs,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
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  • Rui Chen

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
    3. Program in Developmental Biology, Baylor College of Medicine, Houston, Texas
    • Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, MS BCM226, Houston, TX, 77030.
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  • Communicated by William S. Oetting

Abstract

It has been well documented that mutations in the same retinal disease gene can result in different clinical phenotypes due to difference in the mutant allele and/or genetic background. To evaluate this, a set of consanguineous patient families with Leber congenital amaurosis (LCA) that do not carry mutations in known LCA disease genes was characterized through homozygosity mapping followed by targeted exon/whole-exome sequencing to identify genetic variations. Among these families, a total of five putative disease-causing mutations, including four novel alleles, were found for six families. These five mutations are located in four genes, ALMS1, IQCB1, CNGA3, and MYO7A. Therefore, in our LCA collection from Saudi Arabia, three of the 37 unassigned families carry mutations in retinal disease genes ALMS1, CNGA3, and MYO7A, which have not been previously associated with LCA, and 3 of the 37 carry novel mutations in IQCB1, which has been recently associated with LCA. Together with other reports, our results emphasize that the molecular heterogeneity underlying LCA, and likely other retinal diseases, may be highly complex. Thus, to obtain accurate diagnosis and gain a complete picture of the disease, it is essential to sequence a larger set of retinal disease genes and combine the clinical phenotype with molecular diagnosis. 32:1450–1459, 2011. ©2011 Wiley Periodicals, Inc.

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