Nunes M E, Schutt G, Kapur R P, Luthardt F, Kukolich M, Byers P, Evans J P
Department of Pediatrics, University of Washington, Seattle 98195, USA.
Hum Mol Genet. 1995 Nov;4(11):2165-70. doi: 10.1093/hmg/4.11.2165.
Ectrodactyly (split hand/split foot malformation, SHSF) is a human limb malformation characterized by absent central digital rays, deep median cleft, and syndactyly of remaining digits. The disorder is genetically heterogeneous, with at least two loci thus far determined: an autosomal locus at 7q21 designated SHFM1 and an X-linked locus at Xq26 designated SHFM2. Cytogenetic analysis of sporadic SHSF patients and linkage studies in extended pedigrees both suggest more than one autosomal locus exists. We report a novel SHSF locus suggested by a stillborn infant with ectrodactyly and other malformations who inherited an unbalanced translocation resulting in monosomy 4p15.1-4pter and trisomy for 10q25.2-qter. To investigate 10q25 as a possible split hand/split foot locus, microsatellite markers spanning 52 cM of 10q were utilized for linkage analysis of a large autosomal dominant SHSF pedigree in which the region encompassing SHFM1 previously was excluded as containing the causative mutation. The marker D10S583 was fully informative in the family, giving a maximum LOD score of 4.21 at recombination theta = 0.00. Recombination haplotypes define the 9 cM region between D10S541 and D10S574 as inclusive for this second autosomal SHSF locus, for which we propose the designation SHFM3.
缺指（趾）畸形（裂手/裂足畸形，SHSF）是一种人类肢体畸形，其特征为中央指（趾）射线缺失、正中深裂以及其余指（趾）并指（趾）。该疾病在遗传上具有异质性，迄今为止已确定至少两个基因座：位于7q21的常染色体基因座命名为SHFM1，位于Xq26的X连锁基因座命名为SHFM2。散发型SHSF患者的细胞遗传学分析以及扩展家系中的连锁研究均表明存在不止一个常染色体基因座。我们报告了一个新的SHSF基因座，该基因座由一名患有缺指（趾）畸形及其他畸形的死产婴儿所提示，该婴儿遗传了一种不平衡易位，导致4p15.1 - 4pter单体和10q25.2 - qter三体。为了研究10q25作为可能的裂手/裂足基因座，利用跨越10q 52 cM的微卫星标记对一个大型常染色体显性SHSF家系进行连锁分析，在该家系中，先前已排除包含致病突变的SHFM1区域。标记D10S583在该家系中信息完全，在重组θ = 0.00时最大LOD得分为4.21。重组单倍型将D10S541和D10S574之间的9 cM区域定义为这个第二个常染色体SHSF基因座的包含区域，我们提议将其命名为SHFM3。
