title: Bilaterally cleft lip and bilateral thumb polydactyly with triphalangeal component in a patient with two de novo deletions of HSA 4q32 and 4q34 involving PDGFC, GRIA2, and FBXO8 genes.
abstract: We report on a newborn boy with a bilateral cleft of the primary palate, duplicated triphalangeal thumbs, and a patent foramen ovale. During childhood he had moderate developmental delay. Brain MRI at 4 years was normal. The concurrence of non-syndromic clefts of the lip/palate (CL/P) and duplicated thumbs with triphalangeal component has, to our knowledge, not been reported so far. In our case, array-CGH analysis documented two de novo deletions (∼1.2 Mb and ∼400 Kb) of the long arm of chromosome 4, containing four genes: platelet-derived growth factor C (PDGFC), glycine receptor beta subunit (GLRB), glutamate receptor ionotropic AMPA2 (GRIA2), and F-box protein 8 gene (FBXO8). PDGFC codes for a mesenchymal cell growth factor already known to be associated with clefts of the lip. Pdgfc(-/-) mice have skeletal anomalies, and facial schisis resembling human cleft/lip palate. GRIA2 codes for a ligand-activated cation channel that mediates the fast component of postsynaptic excitatory currents in neurons, and may be linked to cognitive dysfunction. FBXO8, a gene of unknown function, is a member of the F-box gene family, among which FBXW4, within the minimal duplicated region associated with human split-hand/foot malformation type 3 (SHFM type 3). The presence of overlapping deletions in patients who do not share the same phenotype of our case suggests incomplete penetrance, and a possible effect of modifier genetic factors.
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Calcia
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gai
authors.forename: Eleonora
authors.initials: E
authors.lastname: Di Gregorio
authors.forename: Flavia
authors.initials: F
authors.lastname: Talarico
authors.forename: Valeria G
authors.initials: VG
authors.lastname: Naretto
authors.forename: Nicola
authors.initials: N
authors.lastname: Migone
authors.forename: Ernesto
authors.initials: E
authors.lastname: Pepe
authors.forename: Enrico
authors.initials: E
authors.lastname: Grosso
authors.forename: Alfredo
authors.initials: A
authors.lastname: Brusco
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000818:Animals; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4; D002971:Cleft Lip / Q000175:diagnosis / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008222:Lymphokines / Q000235:genetics; D008297:Male; D051379:Mice; D010375:Pedigree; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics; D013577:Syndrome; D013933:Thumb / Q000002:abnormalities*
chemical_list: D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D018091:Receptors, AMPA; C411423:platelet-derived growth factor C; C104722:glutamate receptor ionotropic, AMPA 2
keywords: FBXO8; GRIA2; PDGFC; cleft lip; polydactyly; triphalangeal thumb