title: 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).
abstract: 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).
authors.affiliation: Department of Medical Genetics, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ramser
authors.forename: B
authors.initials: B
authors.lastname: Winnepenninckx
authors.forename: C
authors.initials: C
authors.lastname: Lenski
authors.forename: V
authors.initials: V
authors.lastname: Errijgers
authors.forename: M
authors.initials: M
authors.lastname: Platzer
authors.forename: C E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: A
authors.initials: A
authors.lastname: Meindl
authors.forename: R F
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D000595:Amino Acid Sequence; D001530:Belgium; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; C490101:FTSJ1 protein, human; D008780:Methyltransferases