Elliott Alison M, Evans Jane A
Department of Biochemistry and Medical Genetics, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada.
Am J Med Genet A. 2006 Jul 1;140(13):1419-27. doi: 10.1002/ajmg.a.31244.
Split hand foot malformation (SHFM) also known as central ray deficiency, ectrodactyly and cleft hand/foot, is one of the most complex of limb malformations. SHFM can occur as an isolated malformation or in association with other malformations, as in the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and other autosomal dominant conditions with long bone involvement, all showing variable expressivity and reduced penetrance. The deficiency in SHFM patients can also be accompanied by other distal limb anomalies including polydactyly and/or syndactyly. This variability causes the phenotypic classification of SHFM to be far from straightforward and genetic heterogeneity, with at least five loci identified to date, further complicates management of affected patients and their families. Although genotypic-phenotypic correlations have been proposed at the molecular level for SHFM4 patients who have mutations in the P63 gene, phenotypic correlations at the chromosomal level have not been thoroughly documented. Using descriptive epidemiology, Chi square and discriminant function analyses, our laboratory has identified phenotypic patterns associated with the mapped genetic SHFM loci. These findings can assist in classification, provide insight into responsible developmental genes and assist in directing mapping efforts and targeted genetic testing, resulting in more accurate information for family members in the clinical setting. Comparison with relevant animal models is discussed.
裂手裂足畸形（SHFM）也被称为中央射线缺陷、缺指（趾）畸形和裂手/裂足，是最复杂的肢体畸形之一。SHFM可作为一种孤立的畸形出现，或与其他畸形相关联，如在缺指（趾）-外胚层发育不良-裂畸形（EEC）综合征以及其他伴有长骨受累的常染色体显性疾病中，所有这些都表现出可变的表达性和降低的外显率。SHFM患者的缺陷还可能伴有其他远端肢体异常，包括多指（趾）畸形和/或并指（趾）畸形。这种变异性使得SHFM的表型分类远非简单直接，而遗传异质性（迄今已确定至少五个基因座）则进一步使对受影响患者及其家庭的管理复杂化。尽管对于在P63基因中发生突变的SHFM4患者，已在分子水平上提出了基因型-表型相关性，但在染色体水平上的表型相关性尚未得到充分记录。通过描述性流行病学、卡方分析和判别函数分析，我们实验室已确定了与已定位的遗传性SHFM基因座相关的表型模式。这些发现有助于进行分类，深入了解相关的发育基因，并有助于指导定位工作和靶向基因检测，从而在临床环境中为家庭成员提供更准确的信息。文中还讨论了与相关动物模型的比较。
