title: Identification of a novel 15.5 kb SHOX deletion associated with marked intrafamilial phenotypic variability and analysis of its molecular origin.
abstract: Haploinsufficiency of the short stature homeobox contaning SHOX gene has been shown to result in a spectrum of phenotypes ranging from Leri-Weill dyschondrosteosis (LWD) at the more severe end to SHOX-related short stature at the milder end of the spectrum. Most alterations are whole gene deletions, point mutations within the coding region, or microdeletions in its flanking sequences. Here, we present the clinical and molecular data as well as the potential molecular mechanism underlying a novel microdeletion, causing a variable SHOX-related haploinsufficiency disorder in a three-generation family. The phenotype resembles that of LWD in females, in males, however, the phenotypic expression is milder. The 15523-bp SHOX intragenic deletion, encompassing exons 3-6, was initially detected by array-CGH, followed by MLPA analysis. Sequencing of the breakpoints indicated an Alu recombination-mediated deletion (ARMD) as the potential causative mechanism.
authors.affiliation: Cytogenetics and Genomics Department, The Cyprus Institute of Neurology and Genetics, Nicosia 1683, Cyprus. csismani@cing.ac.cy.
authors.forename: Angelos
authors.initials: A
authors.lastname: Alexandrou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papaevripidou
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Tsangaras
authors.forename: Ioanna
authors.initials: I
authors.lastname: Alexandrou
authors.forename: Marios
authors.initials: M
authors.lastname: Tryfonidis
authors.forename: Violetta
authors.initials: V
authors.lastname: Christophidou-Anastasiadou
authors.forename: Eleni
authors.initials: E
authors.lastname: Zamba-Papanicolaou
authors.forename: George
authors.initials: G
authors.lastname: Koumbaris
authors.forename: Vassos
authors.initials: V
authors.lastname: Neocleous
authors.forename: Leonidas A
authors.initials: LA
authors.lastname: Phylactou
authors.forename: Nicos
authors.initials: N
authors.lastname: Skordis
authors.forename: George A
authors.initials: GA
authors.lastname: Tanteles
authors.forename: Carolina
authors.initials: C
authors.lastname: Sismani
mesh_terms: D000328:Adult; D020087:Alu Elements; D001483:Base Sequence; D002871:Chromosome Banding; D056905:Chromosome Breakpoints; D055028:Comparative Genomic Hybridization; D005260:Female; D050172:Genes, X-Linked; D056726:Genetic Association Studies; D006130:Growth Disorders / Q000175:diagnosis / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D000074122:Short Stature Homeobox Protein; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein