title: Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay.
abstract: Mutation screening in neurofibromatosis type 1 (NF1) families has long been hampered by the complexity of the NF1 gene. By using a novel multi-track screening strategy, 67 NF1 families (54 two-generation, 13 three-generation) with a de novo mutation in the germline of the first generation were studied with two extragenic and 11 intragenic markers. The pathological lesion was identified in 31 cases. Loss of heterozygosity (LOH) in the affected individual revealed a gross gene deletion in 15 of the two-generation families; in 12 (80%) of them, the deletion was maternally derived. Eleven patients with a gross deletion exhibited developmental delay, ten had dysmorphic features and six manifested a learning disability. No gross deletion was apparent in any of the 13 three-generation families, suggesting that such lesions are subject to more intense selection. In these families, the new mutation was of paternal origin in 11 kindreds and the underlying mutational event could be characterised in three of them.
authors.affiliation: Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: M
authors.initials: M
authors.lastname: Upadhyaya
authors.forename: M
authors.initials: M
authors.lastname: Ruggieri
authors.forename: J
authors.initials: J
authors.lastname: Maynard
authors.forename: M
authors.initials: M
authors.lastname: Osborn
authors.forename: C
authors.initials: C
authors.lastname: Hartog
authors.forename: S
authors.initials: S
authors.lastname: Mudd
authors.forename: M
authors.initials: M
authors.lastname: Penttinen
authors.forename: I
authors.initials: I
authors.lastname: Cordeiro
authors.forename: M
authors.initials: M
authors.lastname: Ponder
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: M
authors.initials: M
authors.lastname: Krawczak
authors.forename: D N
authors.initials: DN
authors.lastname: Cooper
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics*; D008297:Male; D009035:Mothers; D017253:Neurofibromatoses / Q000235:genetics*; D025542:Neurofibromin 1; D011506:Proteins / Q000235:genetics*
chemical_list: D025542:Neurofibromin 1; D011506:Proteins