title: Compound heterozygosity for a frame shift mutation and a likely pathogenic sequence variant in the planar cell polarity—ciliogenesis gene WDPCP in a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas.
abstract: We report on a young girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. These features are similar to those reported in individuals with variant forms of orofaciodigital syndrome known as congenital heart defects, hamartomas of the tongue and polysyndactly (CHDHTP: OMIM 217085) [Örstavik et al., 1992] and orocardiodigital syndrome [Digilio et al., 1996]. Whole exome sequencing revealed that she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP, a gene that regulates planar cell polarity and ciliogenesis. Results of genotyping in her parents and unaffected siblings were consistent with autosomal recessive inheritance of the mutation and the WDPCP variant. These results suggest that disruption of planar cell polarity and ciliogenesis may result in this unusual form of orofaciodigital syndrome.
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Saari
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovell
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Yu
authors.forename: Gary A
authors.initials: GA
authors.lastname: Bellus
mesh_terms: D019943:Amino Acid Substitution; D001017:Aortic Coarctation / Q000175:diagnosis / Q000235:genetics*; D001706:Biopsy; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006222:Hamartoma / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites; D011859:Radiography; D013576:Syndactyly / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D014062:Tongue Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites
keywords: WDPCP; ciliopathy; coarctation; orofaciodigital syndrome; polysyndactyly; tongue hamartomas