Journal Article

A genomic rearrangement resulting in a tandem duplication is associated with split hand–split foot malformation 3 (SHFM3) at 10q24

Xavier J. de Mollerat, Fiorella Gurrieri, Chad T. Morgan, Eugenio Sangiorgi, David B. Everman, Paola Gaspari, Jeanne Amiel, Michael J. Bamshad, Robert Lyle, Jean-Louis Blouin, Judith E. Allanson, Bernard Le Marec, Melba Wilson, Nancy E. Braverman, Uppala Radhakrishna, Celia Delozier-Blanchet, Albert Abbott, Vincent Elghouzzi, Stylianos Antonarakis, Roger E. Stevenson, Arnold Munnich, Giovanni Neri and Charles E. Schwartz

in Human Molecular Genetics

Volume 12, issue 16, pages 1959-1971
Published in print August 2003 | ISSN: 0964-6906
Published online August 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg212
A genomic rearrangement resulting in a tandem duplication is associated with split hand–split foot malformation 3 (SHFM3) at 10q24

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Split hand–split foot malformation (SHFM) is characterized by hypoplasia/aplasia of the central digits with fusion of the remaining digits. SHFM is usually an autosomal dominant condition and at least five loci have been identified in humans. Mutation analysis of the DACTYLIN gene, suspected to be responsible for SHFM3 in chromosome 10q24, was conducted in seven SHFM patients. We screened the coding region of DACTYLIN by single-strand conformation polymorphism and sequencing, and found no point mutations. However, Southern, pulsed field gel electrophoresis and dosage analyses demonstrated a complex rearrangement associated with a ∼0.5 Mb tandem duplication in all the patients. The distal and proximal breakpoints were within an 80 and 130 kb region, respectively. This duplicated region contained a disrupted extra copy of the DACTYLIN gene and the entire LBX1 and β-TRCP genes, known to be involved in limb development. The possible role of these genes in the SHFM3 phenotype is discussed.

Journal Article.  9666 words.  Illustrated.

Subjects: Genetics and Genomics

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