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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

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
Authors: CALCIA, ALESSANDRO; DI GREGORIO, ELEONORA; NARETTO, VALERIA GIORGIA; MIGONE, Nicola; PEPE, ERNESTO; BRUSCO, Alfredo; Giorgia Gai; Flavia Talarico; Enrico Grosso
Contributors: Alessandro Calcia; Giorgia Gai; Eleonora Di Gregorio; Flavia Talarico; Valeria G. Naretto; Nicola Migone; Ernesto Pepe; Enrico Grosso; Alfredo Brusco
Publication Year: 2013
Collection: Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto)
Subject Terms: FBXO8; GRIA2; PDGFC; polydactyly; triphalangeal thumb; cleft lip
Description: 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.
Document Type: article in journal/newspaper
File Description: STAMPA
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/24038848; info:eu-repo/semantics/altIdentifier/wos/WOS:000327862700036; volume:161A; firstpage:2656; lastpage:2662; numberofpages:7; journal:AMERICAN JOURNAL OF MEDICAL GENETICS. PART A; http://hdl.handle.net/2318/140899; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84884974012
DOI: 10.1002/ajmg.a.36146
DOI: 10.1002/ajmg.a.36146/abstract;jsessionid=22BD29CC8933B5C2FBEB751CC91C08CD.f02t02
Availability: http://hdl.handle.net/2318/140899; https://doi.org/10.1002/ajmg.a.36146; http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.36146/abstract;jsessionid=22BD29CC8933B5C2FBEB751CC91C08CD.f02t02
Rights: info:eu-repo/semantics/closedAccess
Accession Number: edsbas.F2C1F05B
Database: BASE