title: Novel and recurrent EVC and EVC2 mutations in Ellis-van Creveld syndrome and Weyers acrofacial dyostosis.
abstract: Ellis van Creveld syndrome and Weyers acrofacial dysostosis are allelic disorders caused by mutations in EVC or EVC2 genes. We illustrate the results of direct analysis of whole EVC and EVC2 genes' coding regions in 32 unrelated families with clinical diagnosis of Ellis van Creveld syndrome and in 2 families with Weyers acrofacial dysostosis. We identified mutations in 27/32 (84%) cases with Ellis van Creveld syndrome and 2/2 cases with Weyers acrofacial dysostosis. Of the Ellis van Creveld syndrome cases, 20/27 (74%) had a mutation in EVC and 7/27 (26%) in EVC2 genes. The two subjects with Weyers acrofacial dysostosis had a heterozygous mutation in the last exon of EVC2. In total, we detected 25 independent EVC and 11 independent EVC2 mutations. Nineteen EVC mutations (19/25, 76%) and 4 EVC2 mutations (4/11, 36%) were novel. Also one EVC2 gene mutation found in Weyers acrofacial dysostosis was novel. In 5 unrelated cases with a clinical diagnosis of Ellis van Creveld syndrome, we did not find any mutation in either EVC or EVC2 genes. Current findings expand the Ellis van Creveld syndrome and Weyers acrofacial dysostosis mutation spectra, and provide further evidence that the last exon of EVC2 gene is a hot spot for Weyers acrofacial dysostosis mutations. Accordingly, EVC2 exon 22 should be analyzed with priority by mutation screening in individuals with a suspected diagnosis of Weyers acrofacial dysostosis.
authors.affiliation: Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: D'Asdia
authors.forename: Isabella
authors.initials: I
authors.lastname: Torrente
authors.forename: Federica
authors.initials: F
authors.lastname: Consoli
authors.forename: Rosangela
authors.initials: R
authors.lastname: Ferese
authors.forename: Monia
authors.initials: M
authors.lastname: Magliozzi
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Valentina
authors.initials: V
authors.lastname: Guida
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D004613:Ellis-Van Creveld Syndrome / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins; D007438:Introns; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D022821:RNA Splice Sites; D014071:Tooth Abnormalities / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: C406058:EVC protein, human; C473310:EVC2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D022821:RNA Splice Sites