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Abstract：
Split hand/foot malformation (SHFM) or ectrodactyly is a rare congenital disorder affecting limb development characterized by clinical and genetic heterogeneity. SHFM is usually inherited as an autosomal dominant trait with incomplete penetrance. Isolated and syndromic forms are described. The extent of associated malformations is highly variable and multiple syndromes with clinical and genetic overlap have been described. We report here a 28 year-old man presenting with SHFM, sparse hair and widespread freckles. Array-CGH identified a 450 kb de novo 20p12.1 microdeletion encompassing three exons (exon 6 to 8) of MACROD2. Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. Additionally, the deletion encompassed a histone modification H3K27ac mark, known as a provider of quantitative readout of promoter and enhancer activity during human limb development. Altogether, these findings suggest that the 20p12.1 CNV is causative of SHFM in the present case through disturbance of regulatory elements functioning.
摘要：
手/足分裂畸形（SHFM）或外翻畸形是一种罕见的先天性疾病，以临床和遗传异质性为特征，影响肢体发育。SHFM通常作为常染色体显性性状遗传，外显率不完全。描述了孤立和综合征形式。相关畸形的程度是高度可变的，并且已经描述了具有临床和遗传重叠的多种综合征。我们在这里报道一名28岁的男子，稀疏的头发和广泛的雀斑。Array-CGH鉴定出450kb的从头20p12.1微缺失，包含MACROD2的三个外显子（外显子6至8）。尽管MACROD2突变到目前为止还没有与肢体畸形相关，它位于KIF16B旁边，参与成纤维细胞生长因子受体（FGFR）信号传导。此外,删除包含组蛋白修饰H3K27ac标记，被称为人类肢体发育过程中启动子和增强子活性定量读出的提供者。总之,这些发现表明，20p12.1CNV是SHFM的病因，在这种情况下，通过干扰调节元件的功能。
