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Abstract：
Ellis-van Creveld (EvC) syndrome is an autosomal recessive disease, characterized by ectodermal, skeletal, and cardiac anomalies. We report intrafamilial phenotypic variability in three new EvC syndrome cases. Affected males in this study showed only ectodermal abnormalities, whereas an affected female showed the classical presentation of EvC Syndrome, including bilateral postaxial polydactyly of hands and feet, and congenital heart defects. Whole exome sequencing was performed to identify the causative variant, followed by validation and segregation analysis using Sanger sequencing. A homozygous deletion variant (c.731_757del) was identified in exon 6 of the EVC gene (NM_153717.2). The identified variant is considered to be the most likely candidate variant for the EvC syndrome in the family based on previous reports validating the role of EVC variants in the EvC syndrome. The disease correctly segregated in the family members, as all affected members were homozygous, and obligate carriers were heterozygous. Our family is remarkable in highlighting the variable expressivity of the EvC phenotype within the same family, due to a homozygous deletion mutation in the EVC gene. The variable expressivity might be due to the hypomorphic nature of mutation, or the presence of additional variants in modifier genes or in the regulatory regions of the EVC/EVC2 genes.
摘要：
Ellis-vanCreveld（EvC）综合征是一种常染色体隐性疾病，以外胚层为特征，骨骼，和心脏异常.我们报告了三个新的EvC综合征病例的家族内表型变异。在这项研究中，受影响的男性仅显示外胚层异常，而受影响的女性表现出了典型的EvC综合征，包括手和脚的双侧后轴多指，先天性心脏缺陷.进行全外显子组测序以鉴定致病变异，然后使用Sanger测序进行验证和分离分析。在EVC基因(NM_153717.2)的外显子6中鉴定了纯合缺失变体(c.731_757del)。基于先前证实EVC变体在EvC综合征中的作用的报告,所鉴定的变体被认为是家族中的EvC综合征的最可能的候选变体。这种疾病正确地隔离在家庭成员中，因为所有受影响的成员都是纯合的，专性携带者是杂合的。我们的家族在突出同一家族中EvC表型的可变表现力方面非常出色，由于EVC基因中的纯合缺失突变。可变的表现力可能是由于突变的双态性质，或在修饰基因或EVC/EVC2基因的调节区中存在其他变体。
