de Mollerat Xavier J, Gurrieri Fiorella, Morgan Chad T, Sangiorgi Eugenio, Everman David B, Gaspari Paola, Amiel Jeanne, Bamshad Michael J, Lyle Robert, Blouin Jean-Louis, Allanson Judith E, Le Marec Bernard, Wilson Melba, Braverman Nancy E, Radhakrishna Uppala, Delozier-Blanchet Celia, Abbott Albert, Elghouzzi Vincent, Antonarakis Stylianos, Stevenson Roger E, Munnich Arnold, Neri Giovanni, Schwartz Charles E
Center for Molecular Studies, J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC, USA.
Hum Mol Genet. 2003 Aug 15;12(16):1959-71. doi: 10.1093/hmg/ddg212.
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 approximately 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 beta-TRCP genes, known to be involved in limb development. The possible role of these genes in the SHFM3 phenotype is discussed.
裂手裂足畸形（SHFM）的特征是中间手指发育不全/缺如，其余手指融合。SHFM通常为常染色体显性遗传病，人类中已鉴定出至少五个基因座。对怀疑与10q24染色体上的SHFM3相关的DACTYLIN基因进行了突变分析，研究对象为7例SHFM患者。我们通过单链构象多态性和测序筛选了DACTYLIN的编码区，未发现点突变。然而，Southern杂交、脉冲场凝胶电泳和剂量分析表明，所有患者均存在与约0.5 Mb串联重复相关的复杂重排。远端和近端断点分别位于80 kb和130 kb区域内。该重复区域包含一个破坏的DACTYLIN基因额外拷贝以及整个LBX1和β-TRCP基因，已知这些基因参与肢体发育。本文讨论了这些基因在SHFM3表型中的可能作用。
