title: A loss-of-function mutation in the FTSJ1 gene causes nonsyndromic X-linked mental retardation in a Japanese family.
abstract: Mental retardation (MR) is a common trait, affecting approximately 2-3% of individuals in the general population. Although the etiology of MR remains largely unknown, genetics apparently play a major role. Recent molecular studies of X-linked form of MR in European and North American countries have revealed 24 nonsyndromic X-linked mental retardation (NS-XLMR) genes including FTSJ1, a human homolog of the Escherichia coli 2'-O-rRNA methyltransferase FtsJ/RrmJ gene. Here we identified a novel FTSJ1 mutation in an XLMR family through mutation screening of a cohort of 73 unrelated Japanese male probands with MR. Sequence analysis of the proband and his mother revealed a G > A substitution at the consensus for the donor splicing site in intron 8 (c.571 + 1G > A) of FTSJ1. This mutation prevented the removal intron 8 from the pre-mRNA, thereby leading to a frameshift in the mutant FTSJ1 mRNA and resulting in a premature termination in exon 9. Quantitative RT-PCR showed a significant reduction of mutant FTSJ1 mRNA in the patient's lymphoblast cells, which was restored by treatment with cycloheximide, a potent inhibitor of nonsense-mediated mRNA decay (NMD). Therefore, mRNAs carrying this mutation are likely subject to degradation by NMD. Together, loss-of-function of FTSJ1 may be a mechanism for the cognitive dysfunction observed in this family. Our study also suggested that the FTSJ1 mutation probably accounts for XLMR in Japanese at a similar frequency (1-2%) as in Europeans.
authors: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors: Kyoko
authors: K
authors: Takano
authors: Eiji
authors: E
authors: Nakagawa
authors: Ken
authors: K
authors: Inoue
authors: Fumiaki
authors: F
authors: Kamada
authors: Shigeo
authors: S
authors: Kure
authors: Yu-ichi
authors: Y
authors: Goto
mesh_terms: D000293:Adolescent; D044466:Asian People; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D009679:Nuclear Family; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; C490101:FTSJ1 protein, human; D008780:Methyltransferases