title: Definition of minimal duplicated region encompassing the XIAP and STAG2 genes in the Xq25 microduplication syndrome.
abstract: Typical Xq25 duplications are large and associated with heterogeneous phenotypes. Recently, small duplications involving this genomic region and encompassing the GRIA3 and STAG2 genes have been reported. These Xq25 microduplications are associated with a recognizable syndrome including intellectual disability and distinctive facial appearance. We report on Xq25 microduplications in two unrelated families identified by array comparative genomic hybridization. In both families, the genomic imbalances segregated with the disease in male individuals, while the phenotypes of the heterozygous females appeared to be modulated by their X-inactivation pattern. These rearrangements of about 600 kb involved only three genes: THOC2, XIAP, and STAG2. Further characterization by FISH analyses showed tandem duplication in the Xq25 locus of these genes. These data refine the Xq25 candidate region, identifying a minimal duplicated region of about 270 kb encompassing the XIAP and STAG2 genes. We discuss the function of the genes in the rearrangements and their involvement in the pathogenesis of this disorder.
authors.affiliation: Laboratory of Medical Genetics, I.R.C.C.S. Associazione Oasi Maria Santissima, Troina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Benedetto
authors.forename: Sebastiano Antonino
authors.initials: SA
authors.lastname: Musumeci
authors.forename: Emanuela
authors.initials: E
authors.lastname: Avola
authors.forename: Antonino
authors.initials: A
authors.lastname: Alberti
authors.forename: Serafino
authors.initials: S
authors.lastname: Buono
authors.forename: Carmela
authors.initials: C
authors.lastname: Scuderi
authors.forename: Lucia
authors.initials: L
authors.lastname: Grillo
authors.forename: Ornella
authors.initials: O
authors.lastname: Galesi
authors.forename: Angela
authors.initials: A
authors.lastname: Spalletta
authors.forename: Mariangela Lo
authors.initials: ML
authors.lastname: Giudice
authors.forename: Daniela
authors.initials: D
authors.lastname: Luciano
authors.forename: Mirella
authors.initials: M
authors.lastname: Vinci
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Bianca
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Marco
authors.initials: M
authors.lastname: Fichera
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000235:genetics*; D001921:Brain / Q000473:pathology; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D058674:Chromosome Duplication; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005091:Exons; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012729:Sex Chromosome Aberrations; D013577:Syndrome; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*; D055815:Young Adult; D000097722:Cohesins
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C508565:STAG2 protein, human; D000097722:Cohesins
keywords: STAG2; THOC2; XIAP; Xq25 microduplication syndrome; array-CGH