title: Truncation and microdeletion of EVC/EVC2 with missense mutation of EFCAB7 in Ellis-van Creveld syndrome.
abstract: Ellis-van Creveld syndrome (EvC) is a ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. To obtain further insight into the genetics of EvC, we screened EVC/EVC2 mutations in eight Vietnamese EvC patients. All the patients had a congenital heart defect with atypical oral and/or skeletal abnormalities. 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 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 16.4 kb deletion in EVC. This patient also had a heterozygous novel variant in exon 9 of EFCAB7 (c.1171 T > C-p.Y391H), inherited from his father. The atypical cardiac phenotype of this patient and the father suggested that EFCAB7 may modify the phenotype by interacting with EVC. In conclusion, we detected two novel nonsense mutations and a partial deletion of EVC/EVC2 in two Vietnamese families with EvC. Moreover, we found in one family a missense mutation of EFCAB7, a possible modifier gene in EvC and its related disorders.
authors.affiliation: Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.|Children's Hospital 2, Ho Chi Minh City, Vietnam.
authors.forename: Tran Quynh Nhu
authors.initials: TQ
authors.lastname: Nguyen
authors.affiliation: Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.|Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Saitoh
authors.affiliation: Children's Hospital 2, Ho Chi Minh City, Vietnam.
authors.forename: Huu Tung
authors.initials: HT
authors.lastname: Trinh
authors.affiliation: Department of General Internal Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Minh Thien
authors.initials: NM
authors.lastname: Doan
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Seki
authors.affiliation: Department of Pathology and tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology and tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.|Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Kyoto, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuguchi
mesh_terms: D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004613:Ellis-Van Creveld Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D002135:Calcium-Binding Proteins; C406058:EVC protein, human; C473310:EVC2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins
keywords: EVC; EVC2; Ellis-van Creveld; Weyer acrofacial dysostosis; cilopathy