Shyy William, Dietz Frederick, Dobbs Matthew B, Sheffield Val C, Morcuende Jose A
Department of Orthopaedic Surgery and Rehabilitation, University of Iowa, 200 Hawkins Drive, 01023 JPP, Iowa City, IA 52242, USA.
Clin Orthop Relat Res. 2009 May;467(5):1201-5. doi: 10.1007/s11999-008-0701-x. Epub 2009 Jan 22.
Congenital idiopathic clubfoot is a common pediatric musculoskeletal deformity with no known etiology. The deformity reportedly follows a Mendelian pattern of inheritance. Recent work has demonstrated linkage in chromosome 3 and 13 in a large, multigeneration, highly penetrant family with idiopathic clubfoot. From the linkage region on chromosome 3, we selected the candidate genes CAND2 and WNT7a, which are involved in lower extremity development, and hypothesized mutations in these genes would be associated with the phenotype of congenital idiopathic clubfoot. The CAND2 gene was sequenced in 256 clubfoot patients, and 75 control patients, while WNT7a was screened using 56 clubfoot patients and 50 control patients. We found a polymorphism in each gene, but the single nucleotide change in CAND2 was a silent mutation that did not alter the amino acid product, and the single nucleotide change in WNT7a was in the upstream, non-coding or promoter region before the start codon. Based on these results it is unlikely CAND2 and WNT7a are the major genes that causes clubfoot, however WNT7a might be one of many genes that could increase susceptibility to develop clubfoot but do not directly cause it.
先天性特发性马蹄内翻足是一种常见的小儿肌肉骨骼畸形，病因不明。据报道，该畸形遵循孟德尔遗传模式。最近的研究表明，在一个患有特发性马蹄内翻足的大型、多代、高外显率家族中，3号和13号染色体存在连锁关系。从3号染色体的连锁区域中，我们选择了参与下肢发育的候选基因CAND2和WNT7a，并假设这些基因中的突变与先天性特发性马蹄内翻足的表型相关。对256例马蹄内翻足患者和75例对照患者进行了CAND2基因测序，同时对56例马蹄内翻足患者和50例对照患者进行了WNT7a筛查。我们在每个基因中都发现了一个多态性，但CAND2中的单核苷酸变化是一个沉默突变，不会改变氨基酸产物，而WNT7a中的单核苷酸变化位于起始密码子之前的上游非编码或启动子区域。基于这些结果，CAND2和WNT7a不太可能是导致马蹄内翻足的主要基因，然而WNT7a可能是众多可能增加患马蹄内翻足易感性但不直接导致该病的基因之一。
