An analysis of variation in expression of neurofibromatosis (NF) type I (NFI): Evidence for modifying genes

Journal Article · Sun Aug 01 04:00:00 EDT 1993 · American Journal of Human Genetics; (United States)

OSTI ID:5957429

Easton, D F; Ponder, B A.J. ^[1]; Huson, S M ^[2]; Ponder, M A ^[3]

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1. Univ. of Cambridge (United Kingdom)
2. Churchill Hospital, Headington, Oxford (United Kingdom)
3. Institute of Cancer Research, Sutton, Surrey (United Kingdom)

Neurofibromatosis (NF) type 1 (NF1) is notable for its variable expression. To determine whether variation in expression has an inherited component, the authors examined 175 individuals in 48 NF families, including six MZ twin pairs. Three quantitative traits were scored - number of cafe-au-lait patches, number of cutaneous neurofibromas, and head circumference; and five binary traits were scored - the presence or absence of plexiform neurofibromas, optic gliomas, scoliosis, epilepsy, and referral for remedial education. For cafe-au-lait patches and neurofibromas, correlation was highest between MZ twins, less high between first-degree relatives, and lower still between more distant relatives. The high correlation between distant relatives suggests that the type of mutation at the NF1 locus itself plays only a minor role. All of the five binary traits, with the exception of plexiformneurofibromas, also showed significant familial clustering. The familial effects for these traits were consistent with polygenic effects, but there were insufficient data to rule out other models, including a significant effect of different NF1 mutations. There was no evidence of any association between the different traits in affected individuals. The authors conclude that the phenotypic expression of NF1 is to a large extent determined by the genotype at other [open quotes]modifying[close quotes] loci and that these modifying genes are trait specific. 22 refs., 8 tabs.

• OSTI ID: 5957429
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 53:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
BODY
CONNECTIVE TISSUE
DISEASES
GENE MUTATIONS
GENE REGULATION
GENETIC MAPPING
MAPPING
MUTATIONS
NEOPLASMS
NERVE TISSUE
PHENOTYPE
TISSUES