Abstract：
Split-hand/foot malformation (SHFM) with long-bone deficiency (SHFLD) is a rare condition characterized by SHFM associated with long-bone malformation usually involving the tibia. It includes three different types; SHFLD1 (MIM % 119,100), SHFLD2 (MIM % 610,685) and SHFLD3 (MIM # 612576). The latter was shown to be the most commonly reported with a duplication in the 17p13.1p13.3 locus that was narrowed down to the BHLHA9 gene. Here, we report a consanguineous Lebanese family with three members presenting with limb abnormalities including tibial hemimelia. One of these patients presented with additional bowing fibula and another with bilateral split hand. CGH array analysis followed by RQ-PCR allowed us to detect the first homozygous duplication on the short arm of chromosome 17p13.3 including the BHLHA9 gene and involved in SHFLD3. Interestingly, one patient with the homozygous duplicated region, carrying thus four BHLHA9 copies presented with long bone deficiency but no SHFM. The incomplete penetrance and the variable expressivity of the disease in this family as well as the presence of the BHLHA9 homozygous duplication rendered genetic counseling extremely challenging and preimplantation genetic diagnosis almost impossible.
摘要：
伴有长骨缺陷（SHFLD）的手/足畸形（SHFM）是一种罕见的疾病，其特征是SHFM与通常累及胫骨的长骨畸形有关。它包括三种不同的类型；SHFLD1(MIM%119,100)，SHFLD2(MIM%610,685)和SHFLD3(MIM#612576)。后者被证明是最常见的报道，在17p13.1p13.3基因座中有重复，并缩小到BHLHA9基因。这里,我们报告了一个有血缘关系的黎巴嫩家庭,有3名成员出现包括胫骨半角症在内的肢体异常.其中一名患者表现出额外的弯曲腓骨，另一名患者表现出双侧裂手。CGH阵列分析，然后进行RQ-PCR，使我们能够检测到染色体17p13.3短臂上的第一个纯合重复，包括BHLHA9基因并参与SHFLD3。有趣的是,一名具有纯合复制区域的患者，因此携带四个BHLHA9副本，表现为长骨缺陷，但没有SHFM。该家族中疾病的不完全外显率和可变表达率以及BHLHA9纯合复制的存在使遗传咨询极具挑战性，几乎不可能进行植入前遗传诊断。
