Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases. Our findings link this gene to XLMR and shed more light on the pathogenesis of this common disorder.

[1]  M. Sudol,et al.  PQBP-1 (Np/PQ): a polyglutamine tract-binding and nuclear inclusion-forming protein , 2001, Brain Research Bulletin.

[2]  I. Kanazawa,et al.  PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival. , 1999, Human molecular genetics.

[3]  E. Haan,et al.  Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia (MRX2) , 1988, American journal of medical genetics.

[4]  J. Mandel,et al.  Monogenic causes of X-linked mental retardation , 2001, Nature Reviews Genetics.

[5]  I. Kanazawa,et al.  Interaction between Mutant Ataxin-1 and PQBP-1 Affects Transcription and Cell Death , 2002, Neuron.

[6]  R. Lührmann,et al.  Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein. , 1999, Journal of molecular biology.

[7]  K. Iwamoto,et al.  Genomic organization and alternative transcripts of the human PQBP-1 gene. , 2000, Gene.

[8]  Mihoro Saeki,et al.  Association of Two Nuclear Proteins, Npw38 and NpwBP, via the Interaction between the WW Domain and a Novel Proline-rich Motif Containing Glycine and Arginine* , 1999, The Journal of Biological Chemistry.

[9]  I. Kanazawa,et al.  PQBP-1/Npw38, a nuclear protein binding to the polyglutamine tract, interacts with U5-15kD/dim1p via the carboxyl-terminal domain. , 2000, Biochemical and biophysical research communications.

[10]  P. Finan,et al.  A Nuclear SH3 Domain-binding Protein That Colocalizes with mRNA Splicing Factors and Intermediate Filament-containing Perinuclear Networks* , 2001, The Journal of Biological Chemistry.

[11]  A. Komuro,et al.  Npw38, a novel nuclear protein possessing a WW domain capable of activating basal transcription. , 1999, Nucleic acids research.

[12]  E. Mariman,et al.  Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: a new X-linked multiple congenital anomalies/mental retardation syndrome: clinical description and molecular studies. , 1994, American journal of medical genetics.

[13]  J. Gécz,et al.  Nonsyndromic X-linked mental retardation: where are the missing mutations? , 2003, Trends in genetics : TIG.

[14]  M. Midgley.  TRB Culture. The First Farmers of the North European Plain. , 1994 .