Characteristics of intergenerational contractions of the CTG repeat in myotonic dystropy

Journal Article · Tue Mar 01 04:00:00 EST 1994 · American Journal of Human Genetics; (United States)

OSTI ID:7285519

Ashizawa, T; Anvret, M; Grandell, U; Baiget, M; Cobo, A M; Barcelo, J M; Korneluk, R G; Dallapiccola, B; Novelli, G; Fenwick, Jr, R G ^[1]

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1. and others

In myotonic dystropy (DM), the size of a CTG repeat in the DM kinase gene generally increases in successive generations with clinical evidence of anticipation. However, there have also been cases with an intergenerational contraction of the repeat. The authors have examined 1,489 DM parent-offspring pairs, of which 95 (6.4%) showed such contractions in peripheral blood leukocytes (PBL). In 56 of th 95 pairs, clinical data allowed an analysis of their anticipation status. It is surprising that anticipation occurred in 27 (48%) of these 56 pairs, while none clearly showed a later onset of DM in the asymptomatic offspring. The contraction occurred in 76 (10%) of 753 paternal transmission and in 19 (3%) of 736 maternal transmissions. Anticipation was observed more frequently in maternal (85%) than in paternal (37%) transmissions (P<.001). The parental repeat size correlated with the size of intergenerational contraction (r[sup 2] = .50, P [much lt].001), and the slope of linear regression was steeper in paternal ([minus].62) than in maternal ([minus].30) transmissions (P [much lt].001). Sixteen DM parents had multiple DM offspring with the CTG repeat contractions. This frequency was higher than the frequency expected from the probability of the repeat contractions (6.4%) and the size of DM sib population (1.54 DM offspring per DM parent, in 968 DM parents). The authors conclude that (1) intergenerational contraction of the CTG repeat in leukocyte DNA frequently accompanies apparent anticipation, especially when DM is maternally transmitted, and (2) the paternal origin of the repeat and the presence of the repeat contraction in a sibling increase the probability of the CTG repeat contraction. 43 refs., 1 fig., 4 tabs.

• OSTI ID: 7285519
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 54:3; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
DISEASES
ENZYMES
GENE MUTATIONS
HEREDITARY DISEASES
MUSCLES
MUTATIONS
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
TRANSFERASES