Abstract

Complete ascertainment of tuberous sclerosis was attempted in the west of Scotland (population 2,763,000). A total of 101 patients was identified, giving an overall minimum prevalence of 1 in 27,000, but for children under 10 years of age the minimum prevalence was 1 in 12,000. Both parents of 84 of the ascertained cases were assessed for signs of tuberous sclerosis. In 51 pairs of parents no evidence of the condition was seen, indicating that up to 60% of the cases were new mutations. The mutation rate was estimated at 2.5 X 10(-5) mutations per gene per generation. Analysis of parental ages for the new mutations did not show a significant age effect. Thirty-five patients occurred in 13 families containing other affected subjects. The pattern of inheritance was consistent with an autosomal dominant trait in these families. In one sibship, non-penetrance or gonadal mosaicism resulted in affected sibs with normal parents. Of two further sibships where non-penetrance was suspected, one was shown to represent a single new mutation in monozygotic twins and the other to involve non-paternity.