INFLUENCE OF THE SEX OF THE TRANSMITTING GRANDPARENT IN CONGENITAL MYOTONIC-DYSTROPHY

To analyse the influence of the sex of the transmitting grandparents o n the occurrence of the congenital form of myotonic dystrophy (CDM), w e have studied complete three generation pedigrees of 49 CDM cases, an alysing: (1) the sex distribution in the grandparents) generation, and (2) the intergenerational amplification of the CTG repeat, measured i n its absolute and relative values, between grandparents and the mothe rs of CDM patients and between the latter and their CDM children. The mean relative intergenerational increase in the 32 grandparent-mother pairs was significantly greater than in the 56 mother-CDM pairs (Mann- Whitney U test, p<0.001). The mean expansion of the grandfathers (103 CTG repeats) was also significantly different from that seen in the gr andmothers' group (154 CTG repeats) (MannWhitney U test, p<0.01). This excess of non-manifesting males between the CDM grandparents' generat ion with a smaller CTG length than the grandmothers could suggest that the premutation has to be transmitted by a male to reach the degree o f instability responsible for subsequent intergenerational CTG expansi ons without size constraints characteristic of the CDM range.