How to Cite this Article: Yamada K, Fukushi D, Ono T, Kondo Y, Kimura R, Nomura N, Kosaki K-j, Yamada Y, Mizuno S, Wakamatsu N. 2010. Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a patient with mental retardation. Am J Med Genet Part A 152A:3057–3067.
Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a patient with mental retardation†
Article first published online: 17 NOV 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 12, pages 3057–3067, December 2010
How to Cite
Yamada, K., Fukushi, D., Ono, T., Kondo, Y., Kimura, R., Nomura, N., Kosaki, K.-j., Yamada, Y., Mizuno, S. and Wakamatsu, N. (2010), Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a patient with mental retardation. Am. J. Med. Genet., 152A: 3057–3067. doi: 10.1002/ajmg.a.33174
- Issue published online: 23 NOV 2010
- Article first published online: 17 NOV 2010
- Manuscript Accepted: 28 AUG 2009
- Manuscript Received: 8 MAY 2009
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- mental retardation;
- chromosome 20;
- chromatin assembly;
- chromosome alignment
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. © 2010 Wiley-Liss, Inc.