title: A child with mild X-linked intellectual disability and a microduplication at Xp22.12 including RPS6KA3.
abstract: Multiplex ligation-dependent probe amplification (MLPA) and array- comparative genomic hybridization analysis have been proven to be useful in the identification of submicroscopic copy-number imbalances in families with nonsyndromic X-linked intellectual disability (NS-XLID). Here we report the first description of a child with mild intellectual disability and a submicroscopic duplication at Xp22.12 identified by MLPA with a P106 MRX kit (MRC-Holland, Amsterdam, Netherlands) and further confirmed and characterized with a custom 244-k oligo-array, fluorescence in situ hybridization, quantitative polymerase chain reaction (qPCR), and immunoblotting. This 1.05-megabase duplication encompasses 7 genes, RPS6KA3 being the only of these genes known to be related to ID. The proband was an 8-year-old boy referred to the genetics unit for psychomotor retardation and learning disabilities. Both maternal brothers also showed learning difficulties and delayed language during childhood in a similar way to the proband. These boys also carried the duplication, as did the healthy mother and grandmother of the proband. The same duplication was also observed in the 5-year-old younger brother who presented with features of developmental delay and learning disabilities during the previous year. Increased RPS6KA3/RSK2 levels were demonstrated in the proband by qPCR and immunoblotting. To our knowledge, this is the first family identified with a submicroscopic duplication including the entire RPS6KA3/RSK2 gene, and our findings suggest that an increased dose of this gene is responsible for a mild form of NS-XLID.
authors.affiliation: Molecular Genetics Laboratory, Department of Biochemistry, Cruces Hospital, 48903 Barakaldo, Bizkaia, Spain. mariaisabel.tejadaminguez@osakidetza.net
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Tejada
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: Ainhoa
authors.initials: A
authors.lastname: García-Ribes
authors.forename: Susana
authors.initials: S
authors.lastname: Larrucea
authors.forename: Francesco
authors.initials: F
authors.lastname: Acquadro
authors.forename: Juan-C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Stefanie
authors.initials: S
authors.lastname: Belet
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
authors.forename: Maria-Asun
authors.initials: MA
authors.lastname: López-Aríztegui
mesh_terms: D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D015151:Immunoblotting; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D016133:Polymerase Chain Reaction; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics*; D012729:Sex Chromosome Aberrations
chemical_list: D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3