Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1

Abbruzzese, A., Costanzi Porrini, S., Mariani, B., Gould, F.K., McAbney, J.P., Monckton, D.G. , Ashizawa, T. and Giacanelli, M. (2002) Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1. Annals of Neurology, 52(4), 435 -441. (doi: 10.1002/ana.10304)

Abstract

Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG repeat in the DMPK gene on chromosome 19q13.3. We present two siblings with DM1 who each inherited a premutation allele, (CTG)43, stably transmitted from the mother and a full-mutation allele, either (CTG)500 or (CTG)180, derived from a paternal protomutation allele, (CTG)52. Small-pool polymerase chain reaction analysis showed that the (CTG)52 repeat allele was relatively stable in somatic tissues but was highly unstable in the male germline and extremely biased toward further expansion, consistent with the high levels of anticipation observed in DM1 families. The (CTG)43 allele showed subtle somatic instability in the mother, with maximum additions of two repeats and deletions of one repeat. Conversely, in the younger affected siblings the (CTG)43 allele showed a high degree of somatic instability (approximately 70% mutation load), resulting in deletions reverting to the high end of the normal range (down to [CTG]33) and additions up to the proto-mutation range (up to [CTG]64). The difference in the somatic stability of the (CTG)43 allele between the mother and her offspring suggests that interallelic interactions or other mechanisms in trans regulate the stability of the (CTG)43 premutation allele.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McAbney, Mr John and Monckton, Professor Darren
• Authors: Abbruzzese, A., Costanzi Porrini, S., Mariani, B., Gould, F.K., McAbney, J.P., Monckton, D.G., Ashizawa, T., and Giacanelli, M.
• Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry; R Medicine > RC Internal medicine; Q Science > QH Natural history > QH426 Genetics
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Annals of Neurology
• Publisher: John Wiley and Sons, Inc.
• ISSN: 0364-5134
• Copyright Holders: © John Wiley & Sons, Inc.
• First Published: First published in Annals of Neurology 52(4):435-441
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher