Unusual association of a unique CAG interruption in 5' of DM1 CTG repeats with intergenerational contractions and low somatic mosaicism.
Hum Mutat
; 39(7): 970-982, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29664219
ABSTRACT
Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder associated with high variability of symptoms and anticipation. DM1 is caused by an unstable CTG repeat expansion that usually increases in successive generations and tissues. DM1 family pedigrees have shown that â¼90% and 10% of transmissions result in expansions and contractions of the CTG repeat, respectively. To date, the mechanisms of CTG repeat contraction remain poorly documented in DM1. In this report, we identified two new DM1 families with apparent contractions and no worsening of DM1 symptoms in two and three successive maternal transmissions. A new and unique CAG interruption was found in 5' of the CTG expansion in one family, whereas multiple 5' CCG interruptions were detected in the second family. We showed that these interruptions are associated with maternal intergenerational contractions and low somatic mosaicism in blood. By specific triplet-prime PCR, we observed that CTG repeat changes (contractions/expansions) occur preferentially in 3' of the interruptions for both families.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expansão das Repetições de Trinucleotídeos
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Predisposição Genética para Doença
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Mosaicismo
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Distrofia Miotônica
Tipo de estudo:
Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article