Phenotype–Genotype Correlation in Children with Neurofibromatosis Type 1

Abstract

AbstractNeurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an incidence of ∼1 in 4,000 live births. Neurofibromin, the gene product, is ubiquitously expressed at high levels in the nervous system and functions as a tumor suppressor. Haploinsufficiency of neurofibromin through mutation leads to an increased risk of developing benign and malignant tumors in affected individuals. Although NF1 has complete penetrance, it displays considerable inter- and intrafamilial variability in phenotypic expression which poses disease prediction and management problems. Some NF1 genotype–phenotype correlations have been described. To evaluate the genetic component of variable expressivity in NF1, we examined the phenotypic correlations between affected relatives in 52 NF1 patients from 45 families.