SHORT REPORT

A splice site mutation in the methyltransferase gene FTSJ1 in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9)

J Ramser^1,5, B Winnepenninckx², C Lenski¹, V Errijgers², M Platzer⁴, C E Schwartz³, A Meindl^1,5, R F Kooy²

¹ Department of Medical Genetics, Ludwig-Maximilians-University, Munich, Germany
² Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
³ JC Self Research Institute, Greenwood Genetic Center, Greenwood, SC, USA
⁴ Institute for Molecular Biotechnology, Jena, Germany
⁵ Department of Obstetrics and Gynaecology, Technical University, Munich, Germany

Correspondence to:
Correspondence to:
Alfons Meindl
Department of Medical Genetics, Ludwig-Maximilians-University, Goethestrasse 29, 80336 Munich, Germany; alfons{at}pedgen.med.uni-muenchen.de
R Frank Kooy
Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Frank.Kooy{at}ua.ac.be

Mental retardation is the most frequent cause of serious handicap in children and young adults. The underlying causes of this heterogeneous condition are both acquired and genetically based. A recently performed refinement of the linkage interval in a large Belgian family with mild to severe non-syndromic X linked mental retardation, classified as MRX9, revealed a candidate region of 11.3 Mb between markers DXS228 and DXS1204 on the short arm of the X chromosome. In order to identify the underlying disease gene in the MRX9 family, we established a gene catalogue for the candidate region and performed comprehensive mutation analysis by direct sequencing. A human homologue of the bacterial 23S rRNA methyltransferase Fstj, the FTSJ1 gene, is located within this region and displayed a sequence alteration in the conserved acceptor splice site of intron 3 (IVS3-2A>G) in all tested patients and carrier females of this family. In contrast, it was absent in all unaffected male family members tested. The mutation results in skipping of exon 4 and introduces a premature stop codon in exon 5, probably leading to a severely truncated protein. Our finding indicates that a protein, possibly associated with ribosomal stability, can be linked to X linked mental retardation (XLMR).

Abbreviations: SAM, S-adenosylmethionine; XLMR, X linked mental retardation

Keywords: FTSJ domain; mental retardation; methyltransferase; MRX9

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This article has been cited by other articles:

• Raymond, F L (2006). X linked mental retardation: a clinical guide. J. Med. Genet. 43: 193-200 [Abstract] [Full Text]