A novel microdeletion at chromosome 2q31.1-31.2 in a three-generation family presenting duplication of great toes with clinodactyly

Authors

  • L-P Tsai,

    1. Department of Pediatrics, Tzu Chi General Hospital, Xindian, Taipei, Taiwan
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  • H-M Liao,

    1. Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan
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  • Y-J Chen,

    1. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
    2. Department of Teaching and Research, Taipei City Hospital, Taipei, Taiwan
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  • J-S Fang,

    1. Institute of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
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  • C-H Chen

    Corresponding author
    1. Institute of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
    2. Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Zhunan, Taiwan
    3. Graduate Institute of Clinical Medicine, Tzu Chi University, Hualien, Taiwan
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Dr Chen Chia-Hsiang, MD, PhD, Graduate Institute of Clinical Medicine, Tzu Chi University, Hualien City 970, Taiwan.
Tel.: 886 3 8565301x2161;
fax: 886 3 8466863;
e-mail: cchen@mail.tcu.edu.tw

Abstract

HOXD gene cluster maps to chromosome 2q31 and plays a key role in embryonic limb morphogenesis. Mutations of the HOXD13 and HOXD10 genes have been found to be associated with digital and limb malformations. In addition, dysregulation of HOXD gene cluster has been proposed to account for the limb abnormalities in patients with chromosome 2q rearrangements. In this report, we investigated a three-generation family presenting clinical phenotypes of duplication of great toes, tapering fingers, and clinodactyly of the fifth finger in both hands, which were transmitted in a dominant fashion in this family. We identified and validated an interstitial microdeletion of ∼3.4 Mb at chromosome 2q31.1-31.2 by array-based comparative genomic hybridization, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction that cosegregates with the clinical phenotypes in this family. The microdeletion removes 30 labeled genes including the entire HOXD gene cluster, suggesting that the digital abnormalities of this family may be attributed to the haploinsufficiency of the HOXD gene cluster. The delineation of the microdeletion region may contribute to the genotype–phenotype correlation study in patients with genomic rearrangements of the long arm of chromosome 2 and helps to understand the pathogenesis of haploinsufficiency of the HOXD gene cluster.

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