A loss-of-function mutation in the FTSJ1 gene causes nonsyndromic x-linked mental retardation in a Japanese family

Kyoko Takano, Eiji Nakagawa, Ken Inoue, Fumiaki Kamada, Shigeo Kure, Yu Ichi Goto, Johji Inazawa, Mitsuhiro Kato, Takeo Kubota, Kenji Kurosawa, Naomichi Matsumoto, Eiji Nanba, Hitoshi Okazawa, Shinji Saitoh, Takahito Wada

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Mental retardation (MR) is a common trait, affecting ∼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 + IG > 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.

Original languageEnglish
Pages (from-to)479-484
Number of pages6
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number4
Publication statusPublished - 2008 Jun 5


  • Mutation frequency
  • Nonsense-mediated mRNA decay
  • Premature termination codon
  • Splice site mutation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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