Two novel heterozygous mutations of EVC2 cause a mild phenotype of Ellis–van Creveld syndrome in a Chinese family

Abstract

Ellis-van Creveld syndrome (EvC, chondroectodermal dysplasia; OMIM 225500) is an autosomal recessive skeletal dysplasia with associated multisystem involvement. The syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails, and abnormal teeth. Congenital heart defects occur in 50-60% of cases. In this study, we report EvC in a 6-year-old Chinese girl with hypodontia and polydactyly, mild short stature, and abnormalities of the knee joints. No signs of short ribs, narrow thorax, or congenital heart defects were found in this patient. The EvC phenotype shares some similarity with Weyers acrofacial dysostosis (Weyer; OMIM 193530), an autosomal dominant disorder clinically characterized by mild short stature, postaxial polydactyly, nail dystrophy, and dysplastic teeth. Mutations in EVC or EVC2 are associated with both EvC syndrome and Weyers acrodental dysostosis, but the two conditions differ in the severity of the phenotype and their pattern of inheritance. In this study, two novel heterozygous EVC2 mutations, IVS5-2A > G and c.2653C > T (Arg885X), were identified in the patient. The IVS5-2A > G mutation was inherited from the patient's mother and the c.2653C > T from her father. Her parents have no phenotypic symptoms similar to those of the patient. These findings extend the mutation spectrum of this malformation syndrome and provide the possibility of prenatal diagnosis for future offspring in this family.

Association of promoter methylation statuses of congenital heart defect candidate genes with Tetralogy of Fallot

“…EGFR , a receptor tyrosine kinase in the ErbB family, activates several signaling cascades that convert extra-cellular cues into appropriate cellular responses and has been demonstrated to be associated with the congenital left ventricular outflow tract obstruction [31]. EVC2 plays a critical role in bone formation and skeletal development and mutations in EVC2 are associated with Ellis van Creveld syndrome in which 50-60% of congenital heart defects occur [32]. NFATC2 is a DNA binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR).…”

Identification of a novel EVC variant in a Han‐Chinese family with Ellis‐van Creveld syndrome

“…In EVC, biallelic nonsense and/or frameshift mutations in the EVC or EVC2 are likely to result in NMD or truncated proteins, and thus lead to EVC in a loss‐of‐function mechanism. In WAD, mutations in the last exon of EVC2 may escape NMD and the resulted, more stable EVC2 proteins may have a negative effect by gaining a function or affecting the normal protein (Ibarra‐Ramirez et al, ; Shen, Han, Zhang, Zhao, & Feng, ; Shi et al, ; Valencia et al, ).…”

Dual Diagnosis of Ellis-van Creveld Syndrome and Hearing Loss in a Consanguineous Family

“…Interestingly, the 2 patients with compound heterozygous mutations exhibited differing clinical severities. The initial publication identifying the c.2653C>T mutation described this in a compound heterozygous state with an IVS5-2A>G change in a female Chinese patient [Shen et al, 2011]. This patient was described with a mild syndrome that included postaxial polydac- tyly, nail dysplasia, tooth abnormalities, and mild short stature.…”