title: 372 kb microdeletion in 18q12.3 causing SETBP1 haploinsufficiency associated with mild mental retardation and expressive speech impairment.
abstract: Several cases of interstitial deletion encompassing band 18q12.3 are described in patients with mild dysmorphic features, mental retardation and impairment of expressive language. The critical deleted region contains SETBP1 gene (SET binding protein 1). Missense heterozygous mutations in this gene cause Schinzel-Giedion syndrome (SGS, MIM#269150), characterized by profound mental retardation and multiple congenital malformations. Recently, a 18q12.3 microdeletion causing SETBP1 haploinsufficiency has been described in two patients that show expressive speech impairment, moderate developmental delay and peculiar facial features. The phenotype of individual with partial chromosome 18q deletions does not resemble SGS. The deletion defines a critical region in which SETBP1 is the major candidate gene for expressive speech defect. We describe an additional patient with the smallest 18q12.3 microdeletion never reported that causes the disruption of SETBP1. The patient shows mild mental retardation and expressive speech impairment with striking discrepancy between expressive and receptive language skills. He is able to communicate using gestures and mimic expression of face and body with surprising efficacy. The significant phenotypic overlap between this patient and the cases previously reported enforce the hypothesis that SETBP1 haploinsufficiency may have a role in expressive language development.
authors.affiliation: SOD Diagnostica genetica, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Marseglia
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Scordo
authors.forename: Chiara
authors.initials: C
authors.lastname: Pescucci
authors.forename: Genni
authors.initials: G
authors.lastname: Nannetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Biagini
authors.forename: Valeria
authors.initials: V
authors.lastname: Scandurra
authors.forename: Francesca
authors.initials: F
authors.lastname: Gerundino
authors.forename: Alberto
authors.initials: A
authors.lastname: Magi
authors.forename: Matteo
authors.initials: M
authors.lastname: Benelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Torricelli
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D057895:Haploinsufficiency; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007805:Language Development Disorders / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; C425066:SETBP1 protein, human