A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I Prevalence, fitness, mutation rate, and effect of parental transmission on severity

Abstract

A population based study of von Recklinghausen neurofibromatosis in south east Wales (population 668 100) identified 69 families with 135 affected members (prevalance 1/4950 of the population). In these families penetrance of the NF-1 gene was 100% by the age of five years. The genetic fitness of NF-1 sufferers was found to be reduced to 0 47, the effect being more marked in males than females (f=0 31 and 0 60, respectively). Forty-one of 135 cases were judged to represent new disease mutations and the mutation rate was estimated to lie between 3 l×l0-5 and 10 4×l0-5. A parental age effect for new mutations was not found, nor was a maternal effect on disease severity.