Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a patient with mental retardation

Kenichiro Yamada, Daisuke Fukushi, Takao Ono, Yoko Kondo, Reiko Kimura, Noriko Nomura, Ken jiro Kosaki, Yasukazu Yamada, Seiji Mizuno, Nobuaki Wakamatsu

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


CHD6 is an ATP-dependent chromatin-remodeling enzyme, which has been implicated as a crucial component for maintaining and regulating chromatin structure. CHD6 belongs to the largest subfamily, subfamily III (CHD6-9), of the chromodomain helicase DNA (CHD-binding protein) family of enzymes (CHD1-9). Here we report on a female patient with a balanced translocation t(4;20)(q33;q12) presenting with severe mental retardation and brachydactyly of the toes. We identified the translocation breakpoint in intron 27 of CHD6 at 20q12, while the 4q33 breakpoint was intergenic. Northern blot analysis demonstrated the CHD6 mRNA in the patient's lymphoblastoid cells was decreased to ̃50% of the control cells. To investigate the cellular mechanism of diseases resulting from decreased CHD subfamily III proteins, we knocked down CHD6 or CHD7 by RNA interference in HeLa cells and analyzed chromosome alignment. The both CHD6- and CHD7-knockdown cells showed increased frequency of misaligned chromosomes on metaphase plates. Moreover, an elevated frequency of aneuploidy, the major cause of miscarriages and mental retardation, was observed in patients with CHD6 and CHD7 haploinsufficiency. These results suggest that CHD6 and CHD7 play important roles in chromatin assembly during mitosis and that mitotic delay and/or impaired cell proliferation may be associated with pathogenesis of the diseases caused by CHD6 or CHD7 mutations.

Original languageEnglish
Pages (from-to)3057-3067
Number of pages11
JournalAmerican Journal of Medical Genetics, Part A
Volume152 A
Issue number12
Publication statusPublished - 2010 Dec


  • Brachydactyly
  • CHD6
  • CHD7
  • Chromatin assembly
  • Chromosome 20
  • Chromosome alignment
  • Mental retardation
  • Translocation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a patient with mental retardation'. Together they form a unique fingerprint.

Cite this