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.

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Figure 1: Mutations in PQBP1 affecting the AG stretch of the DR/ER repeat.
Figure 2: Subcellular localization of recombinant PQBP1 (red), Brn-2 (green) and of truncated mutant PQBP1 (red) proteins in Neuro2A cells.

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We thank I. van der Burgt, C. de Die-Smulders, R. Robledo and M. Siniscalco for providing blood from affected individuals; M. Vingron for discussion; R. Reinhardt for support with mutation search; R. McEvilly for the rat Brn-2 cDNA clone; H. Madle and S. Freier for establishing lymphoblastoid cell lines; P. Nierle for help in the initial stage of the mutation screening; and M. Klein, V. Suckow, Z. Kijas, B. Lipkowitz, K. Lower, O. Mckenzie, S. Kübart and M. Mangelsdorf for technical assistance. This work was supported by a grant from the Australian National Health and Medical Research Council to J.G., by the Deutsches Humangenom-Programm, by the Nationales Genomforschungsnetzwerk and by the 5th EU Framework.

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Correspondence to Vera M Kalscheuer.

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Kalscheuer, V., Freude, K., Musante, L. et al. Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation. Nat Genet 35, 313–315 (2003).

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