How to cite this article: Musova Z, Mazanec R, Krepelova A, Ehler E, Vales J, Jaklova R, Prochazka T, Koukal P, Marikova T, Kraus J, Havlovicova M, Sedlacek Z. 2009. Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene. Am J Med Genet Part A 149A:1365–1374.
Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene†
Version of Record online: 9 JUN 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 7, pages 1365–1374, July 2009
How to Cite
Musova, Z., Mazanec, R., Krepelova, A., Ehler, E., Vales, J., Jaklova, R., Prochazka, T., Koukal, P., Marikova, T., Kraus, J., Havlovicova, M. and Sedlacek, Z. (2009), Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene. Am. J. Med. Genet., 149A: 1365–1374. doi: 10.1002/ajmg.a.32987
- Issue online: 18 JUN 2009
- Version of Record online: 9 JUN 2009
- Manuscript Accepted: 26 MAY 2009
- Manuscript Received: 16 JAN 2009
- Ministry of Health of the Czech Republic. Grant Number: MZO00064203
- myotonic dystrophy;
- CTG repeat;
- DMPK gene
Myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in the 3′ UTR of the DMPK gene. A length exceeding 50 CTG triplets is pathogenic. Intermediate alleles with 35–49 triplets are not disease-causing but show instability in intergenerational transmissions. We report on the identification of multiple patients with different patterns of CCG and CTC interruptions in the DMPK CTG repeat tract that display unique intergenerational instability. In patients bearing interrupted expanded alleles, the location of the interruptions changed dramatically between generations and the repeats tended to contract. The phenotype for these patients corresponded to the classical form of the disease, but in some cases without muscular dystrophy and possibly with a later onset than expected. Symptomatic patients bearing interrupted intermediate length repeat tracts were also identified, although the role of the interruptions in their phenotype remains unclear. The identification of interruptions in the DMPK repeat has important consequences for molecular genetic testing where they can lead to false negative conclusions. © 2009 Wiley-Liss, Inc.