PT - JOURNAL ARTICLE AU - J Ramser AU - B Winnepenninckx AU - C Lenski AU - V Errijgers AU - M Platzer AU - C E Schwartz AU - A Meindl AU - R F Kooy TI - A splice site mutation in the methyltransferase gene <em>FTSJ1</em> in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9) AID - 10.1136/jmg.2004.019000 DP - 2004 Sep 01 TA - Journal of Medical Genetics PG - 679--683 VI - 41 IP - 9 4099 - http://jmg.bmj.com/content/41/9/679.short 4100 - http://jmg.bmj.com/content/41/9/679.full SO - J Med Genet2004 Sep 01; 41 AB - 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&gt;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).