An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes.

摘要: Neurofibromatosis (NF) type 1 (NF1) is notable for its variable expression. To determine whether variation in expression has an inherited component, we examined 175 individuals 48 NF families, including six MZ twin pairs. Three quantitative traits were scored--number of cafe-au-lait patches, number cutaneous neurofibromas, and head circumference; five binary scored--the presence or absence plexiform optic gliomas, scoliosis, epilepsy, referral remedial education. For patches correlation was highest between twins, less high first-degree relatives, lower still more distant relatives. The twins suggests a strong genetic component expression, but the low relatives that mutation at NF1 locus itself plays only minor role. All traits, with exception also showed significant familial clustering. effects these consistent polygenic effects, there insufficient data to rule out other models, effect different mutations. There no evidence any association affected individuals. We conclude phenotypic large extent determined by genotype "modifying" loci modifying genes are trait specific.