title: Interstitial 16p13.3 microduplication: case report and critical review of genotype-phenotype correlation.
abstract: We report on a patient with a recognizable phenotype of intellectual disability, multiple congenital anomalies, musculoskeletal anomalies and craniofacial dysmorphisms, carrying a de novo 0.4 Mb duplication of chromosome region 16p13.3 detected by SNP-array analysis. In addition, myopia, microcephaly and growth retardation were observed. The causal 16p13.3 duplication is one of the smallest reported so far, and includes the CREB binding protein gene (CREBBP, MIM 600140), whose haploinsufficiency is responsible for the Rubinstein-Taybi syndrome, and the adenylate cyclase 9 gene (ADCY9, MIM 603302). By comparing the clinical manifestations of our patient with those of patients carrying similar rearrangements, we confirmed that 16p13.3 microduplications of the Rubinstein-Taybi region result in a recognizable clinical condition that likely represents a single gene disorder. In addition, our case allowed us to define with more precision the smallest region of overlap (SRO) in all patients reported so far, encompassing only the CREBBP gene, and is useful to confirm and further define the phenotypic characteristics due to duplication of the CREBBP gene, being the first case of interstitial duplication with microcephaly and growth defects reported to date.
authors.affiliation: Medical Genetics University of Catania, Department of Pediatrics Building 4, Via Santa Sofia 78, 95123 Catania, Italy. mattina@unict.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Mattina
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Stallone
authors.forename: Rita Maria
authors.initials: RM
authors.lastname: Pulvirenti
authors.forename: Laura
authors.initials: L
authors.lastname: Di Dio
authors.forename: Piero
authors.initials: P
authors.lastname: Pavone
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pavone
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002871:Chromosome Banding; D058674:Chromosome Duplication; D002885:Chromosomes, Human, Pair 16; D019066:Facies; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011859:Radiography