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A novel ZRS mutation in a Balochi tribal family with triphalangeal thumb, pre-axial polydactyly, post-axial polydactyly, and syndactyly

Authors

  • Julia E. VanderMeer,

    1. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California
    2. Institute for Human Genetics, University of California San Francisco, San Francisco, California
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    • Julia E VanderMeer and Muhammad Afzal contributed equally to this work.

  • Muhammad Afzal,

    1. Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan
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    • Julia E VanderMeer and Muhammad Afzal contributed equally to this work.

  • Saadia Alyas,

    1. Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan
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  • Sayedul Haque,

    1. Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan
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  • Nadav Ahituv,

    Corresponding author
    1. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California
    2. Institute for Human Genetics, University of California San Francisco, San Francisco, California
    • 513 Parnassus Ave, HSE 901H, Box 0794, San Francisco, CA 94143.
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  • Sajid Malik

    Corresponding author
    1. Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan
    • Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, 45320 Islamabad, Pakistan.
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  • How to Cite this Article: VanderMeer JE, Afzal M, Alyas S, Haque S, Ahituv N, Malik S. 2012. A novel ZRS mutation in a balochi tribal family with triphalangeal thumb, pre-axial polydactyly, post-axial polydactyly, and syndactyly. Am J Med Genet Part A. 158A:2031–2035.

Abstract

Limb malformations are one of the most common types of human congenital malformations. Mutations in the ZRS enhancer of Sonic Hedgehog are thought to be responsible for pre-axial polydactyly in multiple independent families. Here, we describe a large Balochi tribal family from Southern Punjab, Pakistan, with a variable set of limb malformations and a novel ZRS mutation. The family has a limb phenotype characterized by triphalangeal thumb, pre-axial polydactyly, and post-axial polydactyly. There is also a high degree of phenotypic heterogeneity with less common clinical findings in the affected family members that include osseous syndactyly of forth–fifth fingers, clinodactyly, hypoplasia of mesoaxial fingers, and bifid halluces. The presentation in most of the affected patients was bilateral and symmetrical. A heterozygous C>A mutation at position 287 of the ZRS enhancer (chr7:156,584,283; hg19) was detected in all affected subjects and is absent from four unaffected family members, 42 unrelated samples, and multiple databases of human variation. Combined, these results identify a novel ZRS287 C>A mutation which leads to a variable spectrum of limb phenotypes. © 2012 Wiley Periodicals, Inc.

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