title: Inv(X)(p21.1;q22.1) in a man with mental retardation, short stature, general muscle wasting, and facial dysmorphism: clinical study and mutation analysis of the NXF5 gene.
abstract: We describe a 59-year-old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X-chromosome: inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle wasting, and facial dysmorphism. Until now, no other patients with similar clinical features have been described in the literature. Molecular analysis of both breakpoints led to the identification of a novel "Nuclear RNA export factor" (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and its neighboring homologue, the NXF2 gene was performed in 45 men with various forms of syndromic X-linked MR (XLMR) and in 70 patients with nonspecific XLMR. In the NXF5 gene four nucleotide changes: one intronic, two silent, and one missense (K23E), were identified. In the NXF2 gene two changes (one intronic and one silent) were found. Although none of these changes were causative mutations, we propose that NXF5 is a good candidate gene for this syndromic form of XLMR, given the suspected role of NXF proteins is within mRNA export/transport in neurons. Therefore, mutation screening of the NXF gene family in phenotypically identical patients is recommended.
authors.affiliation: Human Genome Laboratory and Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium.
authors.forename: Suzanna G M
authors.initials: SG
authors.lastname: Frints
authors.forename: Lin
authors.initials: L
authors.lastname: Jun
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Rudi
authors.initials: R
authors.lastname: Teulingkx
authors.forename: Lut
authors.initials: L
authors.lastname: Van den Berghe
authors.forename: Bernice
authors.initials: B
authors.lastname: De Vos
authors.forename: Martine
authors.initials: M
authors.lastname: Borghgraef
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Vincent
authors.initials: V
authors.lastname: Des Portes
authors.forename: Hans
authors.initials: H
authors.lastname: Van Bokhoven
authors.forename: Ben
authors.initials: B
authors.lastname: Hamel
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Vera
authors.initials: V
authors.lastname: Kalscheuer
authors.forename: Martine
authors.initials: M
authors.lastname: Raynaud
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D041321:Chromosomes, Human, X; D003001:Cloning, Molecular; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D029543:Nucleocytoplasmic Transport Proteins; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013577:Syndrome
chemical_list: C443839:NXF5 protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D012313:RNA