Clinical & Experimental Cardiology
Open Access

Truncation and microdeletion of EVC2 with a novel EFCAB7 missense mutation in rare syndromic congenital heart defects: Ellis-Van Creveld syndrome

6^th International Conference on Clinical & Experimental Cardiology

November 30-December 02, 2015 San Antonio, USA

Tran Quynh Nhu Nguyen1,3, Makiko Saitoh1,2, Huu Tung Trinh3 and Masashi Mizuguchi1,2

1-2The University of Tokyo, Japan 3Children�s Hospital 2, Vietnam

Posters-Accepted Abstracts: J Clin Exp Cardiolog

Abstract :

Ellis-van Creveld syndrome (EvC) belongs to ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. Approximately 60% of EvC patients had severe Congenital Heart Defects (CHD), in which more than half are atrio-ventricular septal defect and common atrium, which leads to early childhood mortality. However, the EvC phenotype overlaps with other ciliopathies, which hampers the accurate diagnosis. To elucidate the genetic characteristics we screened EVC/EVC2 mutations in 8 Vietnamese EvC patients. All showed CHD. One had compound heterozygous EVC2 mutations: a novel mutation c.769G>T-p.E177X in exon 6 inherited from father and another previously reported c.2476C>T-p. R826X mutation in exon 14 inherited from mother. The EVC2 mRNA expression level was significantly lower in the patient and her parents compared to those in the controls. Another case had a novel heterozygous EVC mutation (c.1717C>G-p. S572X) in exon 12, inherited from his father. Of note, the mother without any EVC mutation on Sanger sequencing showed a lower expression level of EVC mRNA compared with controls. SNP array analysis revealed that the patient and mother had a heterozygous 16kb deletion in EVC. This patient also had a heterozygous novel variant in exon 9 of EFCAB7 (c.1171T>C-p. Y391H), inherited from his father. The patient had atypical phenotype, which suggested that EFCAB7 may modify the cardiac malformations by tethering with EVC. In conclusion, we detected two novel nonsense mutations and a partial deletion of EVC/ EVC2 in two families diagnosed as EvC. The relative expression of EVC/EVC2 mRNA was reduced in these members, which revealed that these mutations were disease-causative. Moreover, we showed a possible modifier gene mutation in one family with EvC.

Biography :

Email: qnhu13@m.u-tokyo.ac.jp