Correlation Between Illness Severity and Mutation Source in Neurofibromatosis Type 1 (Nf1) in An infant Population

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, with 100% of penetrance. New mutations rate varies about 25 to 50%. Its frequency is about 1/2500 to 1/3000 newborns. The gene has been located in 17q11.2 but the function of the responsible protein remains unknown. Some authors suggested that inheritance through affected mothers would cause more severe illness. The purpose of the study was to determine the new mutations' ratio in a pediatric population, and the correlation between tumor's type, clinical severity and the origin of mutation (father, mother or new mutation). The study population consisted of 154 children from 97 familes, which attended the Genetics Department from January 1989 to January 1995. They presented NF1 according to the Consensus Development Conference (1988) criteria. 6 patients were excluded because they had a different type of NF and 9 patients because we could not define the way of inheritance or the illness severity degree. Degree of severity was determined by Miller's criteria (1979). Age of the group was 3mo to 18 y (mean 6.24y). M/F ratio: 1.17, 40% were new mutations: 36.4% were due to mother's inheritance and 22.7% to father's inheritance. There were no significant differences in illness severity and the type of tumors between the three groups compared. The present study allows us to conclude that severity of this affection depend on the mutation origin.