Mutations in von Recklinghausen neurofibromatosis: An hypothesis

Abstract

Von Recklinghausen neurofibromatosis or neurofibromatosis type I (NF1) is relatively frequent (1/3,000 livebirths) autosomal dominant condition. Some unusual aspects are noted in this disorder: new mutations are frequent and almost all are of paternal origin without parental age effect. The recurrence of NF1 among children of healthy parents is rare as opposed to other dominant disorders. I propose that in NF1 (1) new mutations occur often in somatic cells or in late germinal cells, however, they occur very rarely in early germinal cells leadding to germinal mosaicism and (2) the individual with somatic mosaicism presents symptoms of the disease. Therefore, an NF1 patient with an apparent new mutation is often a somatic mosaic for the mutation and if the mosaic is alo present in germinal cells some of his children will be affected. This hypotesis may explain the unusual aspects of mutation in NF1.