Identification and characterization of 5' CCG interruptions in complex DMPK expanded alleles

Botta, A., Rossi, G., Marcaurelio, M., Fontana, L., D'Apice, M. R., Brancati, F., Massa, R., Monckton, D. G. , Sangiuolo, F. and Novelli, G. (2017) Identification and characterization of 5' CCG interruptions in complex DMPK expanded alleles. European Journal of Human Genetics, 25(2), pp. 257-261. (doi:10.1038/ejhg.2016.148) (PMID:27876818)

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Abstract

Myotonic dystrophy type 1 is a multisystemic autosomal dominant disorder caused by the expansion of (CTG) n triplets in the 3'UTR of the DMPK gene, on chromosome 19q13.3. In the last years, few DM1 patients with different patterns of CCG/CTC interruptions at the 3′ end of the DMPK expanded tract have been described. However, the role of these interruptions in DM1 pathogenesis is still unclear. To study the frequency, stability and the structure of DMPK variant expanded alleles in the Italian population, we have re-evaluated 254 Italian DM1 patients using triplet-primed PCR (TP-PCR), at both the 3′ and 5′ ends of the CTG expansion. In addition, three DM1 families were also investigated in order to analyze the intergenerational stability of the interrupted DMPK alleles. Fourteen DM1 patients showed a TP-PCR electrophoretic profile indicating CCG/CTC interruptions within the CTG expansion. Interestingly, interruptions have been detected and, for the first time, sequenced at the 5′ end of the CTG array. Analysis of five intergenerational transmissions revealed a substantial intrafamilial stability of the DM1 mutation among relatives. Our results support the hypothesis that CCG/CTC interruptions within the DMPK expanded alleles have a stabilizing effect on the mutational dynamics and can modulate the severity of symptoms in DM1 patients.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Monckton, Professor Darren
Authors: Botta, A., Rossi, G., Marcaurelio, M., Fontana, L., D'Apice, M. R., Brancati, F., Massa, R., Monckton, D. G., Sangiuolo, F., and Novelli, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:European Journal of Human Genetics
Publisher:Nature Publishing Group
ISSN:1018-4813
ISSN (Online):1476-5438
Published Online:23 November 2016

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