title: Unexpected phenotype in a boy with trisomy of the SHOX gene.
abstract: The assessment that heterozygous SHOX mutations leading to SHOX haploinsufficiency play a role in patients with idiopathic short stature (ISS) is already documented in the literature as well as the suggestion that additional copies of SHOX are strongly implicated in a condition of tall stature. However, we report the first case of short stature in a male associated with the presence of three copies of the SHOX gene. Through chromosomal analysis, using Multiplex Ligation-dependent Probe Amplification method of SHOX salsa P018B kit and microsatellite analysis, we identify a new interstitial isolated duplication of the SHOX gene and its enhancer caused by a larger duplication of the PAR1 region in a boy with ISS. Consequently, we propose the hypothesis that this chromosome re-arrangement disrupts the regular interaction between the enhancer and promoter, resulting in a transcription block, thus producing a lack of gene activation, causing the clinical feature of short stature.
authors.affiliation: Department of Pediatrics, University of Modena & Reggio Emilia, Modena, Italy. iughetti.lorenzo@unimore.it
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Iughetti
authors.forename: Lucia
authors.initials: L
authors.lastname: Capone
authors.forename: Heba
authors.initials: H
authors.lastname: Elsedfy
authors.forename: Roberto
authors.initials: R
authors.lastname: Bertorelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Predieri
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Antonino
authors.initials: A
authors.lastname: Forabosco
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Kholy
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D001827:Body Height; D001846:Bone Development / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D006130:Growth Disorders / Q000000981:diagnostic imaging / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D011859:Radiography; D000074122:Short Stature Homeobox Protein; D014314:Trisomy / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein