title: Neurofibromatosis type 1 in two siblings due to maternal germline mosaicism.
abstract: Neurofibromatosis type 1 (NF1) is caused by loss of function mutations of the NF1 gene, which are de novo in 50% of cases. Although this gene shows one of the highest mutation rates in the human genome, germline mosaicism is very rare in this condition. We describe the molecular analysis of a family in which neurofibromatosis type 1 occurred in two out of four siblings born to unaffected parents. Molecular analysis of the NF1 gene identified in both patients the same splicing mutation c.1392+1G>A, which was absent in parental lymphocytes. Microsatellite analysis showed that the two affected siblings shared the same maternal allele, however a specific PCR-RFLP assay excluded the presence of the NF1 splicing mutation in multiple maternal tissues. Our molecular and clinical findings are consistent with a germline mosaicism for the NF1 splicing mutation. This is the first case of maternal germline mosaicism for a NF1 mutation characterized so far at the molecular level. Our data confirm that germline mosaicism is rare in neurofibromatosis 1, but it has important implications for genetic counseling.
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Trevisson
authors.forename: M
authors.initials: M
authors.lastname: Forzan
authors.forename: L
authors.initials: L
authors.lastname: Salviati
authors.forename: M
authors.initials: M
authors.lastname: Clementi
mesh_terms: D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D009030:Mosaicism; D009456:Neurofibromatosis 1 / Q000209:etiology / Q000235:genetics*; D025542:Neurofibromin 1 / Q000235:genetics*; D010375:Pedigree; D035781:Siblings
chemical_list: D025542:Neurofibromin 1
keywords: NF1; germline mosaicism; neurofibromatosis type 1; segmental NF1