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).
- SAM, S-adenosylmethionine
- XLMR, X linked mental retardation
- FTSJ domain
- mental retardation
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This work was supported by grants from the German Ministry for Research and Education (BMBF, 01KW9974) and the European community (EC, QLG2-CT-1999-00791) to AM and by grants from the Belgian National Fund for Scientific Research - Flanders (FWO) and an Interuniversity Attraction Poles Program (IUAP-V) to BW and RFK and a grant from NICHD (HD26202) to CES.
Conflict of interest: none declared.
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