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.
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.
Frints
Suzanna G M
SG
Human Genome Laboratory and Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium.
Jun
Lin
L
Fryns
Jean-Pierre
JP
Devriendt
Koen
K
Teulingkx
Rudi
R
Van den Berghe
Lut
L
De Vos
Bernice
B
Borghgraef
Martine
M
Chelly
Jamel
J
Des Portes
Vincent
V
Van Bokhoven
Hans
H
Hamel
Ben
B
Ropers
Hans-Hilger
HH
Kalscheuer
Vera
V
Raynaud
Martine
M
Moraine
Claude
C
Marynen
Peter
P
Froyen
Guy
G
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
C443839:NXF5 protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D012313:RNA