Deletions spanning the neurofibromatosis 1 gene: identification and phenotype of five patients.

摘要: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by marked variation in clinical severity. To investigate the contribution to variability genes either contiguous or contained within NF1 gene, we screened six patients with mild facial dysmorphology, mental retardation, and/or learning disabilities, for DNA rearrangement of region. Five had gene deletions on basis quantitative densitometry, locus hemizygosity, and analysis somatic cell hybrid lines. Analyses lines carrying each patient's chromosomes 17, 15 regional markers, demonstrated that five carried a deletion > 700 kb size. Minimally, involved entire 350-kb gene; three genes--EVI2A, EVI2B, OMG--that are intron; considerable flanking DNA. For four patients, mapped same interval; fifth patient was larger, extending farther both directions. The remaining allele presumably produced functional neurofibromin; no rearrangements were detected, RNA-PCR it transcribed. These data provide compelling evidence results from haploid insufficiency neurofibromin. Of documented de novo cases, two paternal one maternal allele. parental origin single expressed dramatic effect phenotype. exhibited variable number physical anomalies not correlated extent their deletion. All remarkable exhibiting large neurofibromas age, suggesting unknown region may affect tumor initiation development.