Clinical expression of Ellis‐van Creveld syndrome (EvC) is variable and mild phenotypes have been described, including patients with mostly cardiac and limb involvement. Whether these cases are part of the EvC phenotypic spectrum or separate conditions is disputed. Herein, we describe a family with vertical transmission of atrioventricular canal defect (AVCD), common atrium, and postaxial polydactyly. Targeted sequencing of EVC, EVC2, WDR35, DYNC2LI1, and DYNC2H1 identified different compound heterozygosity in EVC genotypes in the two affected members, consisting of a nonsense (p.Arg622Ter) and a missense (p.Arg663Pro) variant in the father, and the same nonsense variant and a noncanonical splice‐site in‐frame change (c.1316–7A>G) in the daughter. Complementary DNA sequencing, immunoblot, and immunofluorescence experiments using patient‐derived fibroblasts and Evc^–/– mouse embryonic fibroblasts showed that p.Arg622Ter is a loss‐of‐function mutation, whereas p.Arg663Pro and the splice‐site change c.1316–7A>G are hypomorphic variants resulting in proteins that retain, in part, the ability to complex with EVC2. Our molecular and functional data demonstrate that at least in some cases the condition characterized as “common atrium/AVCD with postaxial polydactyly” is a mild form of EvC due to hypomorphic EVC mutations, further supporting the occurrence of genotype‐phenotype correlations in this syndrome.

中文翻译：

---

常见的心房/房室管缺损和轴后多指畸形：一种由 EVC 基因亚型突变引起的 Ellis-van Creveld 综合征的轻度临床亚型。

Ellis-van Creveld 综合征 (EvC) 的临床表现是可变的，并且已经描述了轻微的表型，包括主要是心脏和四肢受累的患者。这些病例是 EvC 表型谱的一部分还是单独的条件存在争议。在此，我们描述了一个具有垂直传播的房室管缺损 (AVCD)、共同心房和轴后多指畸形的家族。的靶向测序EVC，EVC2，WDR35，DYNC2LI1和DYNC2H1中识别不同的化合物杂EVC两个受影响成员的基因型，包括父亲的无义（p.Arg622Ter）和错义（p.Arg663Pro）变异，以及相同的无义变异和非规范剪接位点框内变化（c.1316-7A） >G) 在女儿身上。使用患者来源的成纤维细胞和Evc ^–/–小鼠胚胎成纤维细胞进行的互补 DNA 测序、免疫印迹和免疫荧光实验表明 p.Arg622Ter 是一种功能丧失突变，而 p.Arg663Pro 和剪接位点改变 c.1316– 7A>G 是亚形变体，导致蛋白质部分保留与 EVC2 复合的能力。我们的分子和功能数据表明，至少在某些情况下，特征为“具有轴后多指畸形的共同心房/AVCD”的病症是一种轻度形式的 EvCEVC突变，进一步支持该综合征中基因型-表型相关性的发生。