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.European Journal of Human Genetics advance online publication, 23 November 2016; doi:10.1038/ejhg.2016.148.

Botta, A., Rossi, G., Marcaurelio, M., Fontana, L., D'Apice, M., Brancati, F., et al. (2017). Identification and characterization of 5' CCG interruptions in complex DMPK expanded alleles. EUROPEAN JOURNAL OF HUMAN GENETICS, 25(2), 257-261 [10.1038/ejhg.2016.148].

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

BOTTA, ANNALISA;MASSA, ROBERTO;SANGIUOLO, FEDERICA CARLA;NOVELLI, GIUSEPPE
2017

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.European Journal of Human Genetics advance online publication, 23 November 2016; doi:10.1038/ejhg.2016.148.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/03 - Genetica Medica
Settore MED/26
English
Con Impact Factor ISI
Botta, A., Rossi, G., Marcaurelio, M., Fontana, L., D'Apice, M., Brancati, F., et al. (2017). Identification and characterization of 5' CCG interruptions in complex DMPK expanded alleles. EUROPEAN JOURNAL OF HUMAN GENETICS, 25(2), 257-261 [10.1038/ejhg.2016.148].
Botta, A; Rossi, G; Marcaurelio, M; Fontana, L; D'Apice, M; Brancati, F; Massa, R; G. Monckton, D; Sangiuolo, Fc; Novelli, G
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
Botta et al 2016.pdf

non disponibili

Licenza: Non specificato
Dimensione 421.75 kB
Formato Adobe PDF
421.75 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/169501
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 25
social impact