title: Variable expressivity of a familial 1.9 Mb microdeletion in 3q28 leading to haploinsufficiency of TP63: Refinement of the critical region for a new microdeletion phenotype.
abstract: We report on a 3-year-old male with intellectual disability (ID), characteristic facial features, polydactyly and epilepsy carrying a paternally inherited 3q28 deletion of 1.9 Mb. The father, carrying the same deletion, presents with cleft palate, nail dystrophy and learning difficulties. The deleted region in this family is one of the smallest so far reported among genomic deletions affecting 3q27-3q28 for which some phenotypic descriptions are available. In particular, since the phenotype of our proband is strikingly similar to that previously described in a patient with a 9.3 Mb deletion, the deletion identified in this report contributes to the definition of the molecular boundaries of a genomic region responsible for a distinct clinical phenotype. Within the deleted interval there are 9 annotated genes, including TP63. Gain of function mutations of TP63 are known to be responsible for a group of conditions with distal limb and ectodermal involvement, such as ADULT, EEC, LMS, and SHFM4 syndromes. Interestingly, our cases demonstrate a milder phenotypic effect for loss of function of this gene.
authors.affiliation: Institute of Medical Genetics, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ponzi
authors.affiliation: Institute of Medical Genetics, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Asaro
authors.affiliation: Institute of Medical Genetics, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Orteschi
authors.affiliation: Institute of Medical Genetics, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Genuardi
authors.affiliation: Institute of Medical Genetics, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.affiliation: Institute of Medical Genetics, Università Cattolica S. Cuore, Rome, Italy. Electronic address: fgurrieri@rm.unicatt.it.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Gurrieri
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019066:Facies; D057895:Haploinsufficiency; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D017689:Polydactyly / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: 3q28 deletion; Intellectual disability; TP63