title: Germline mosaicism in neurofibromatosis type 1 due to a paternally derived multi-exon deletion.
abstract: We report on the clinical and molecular features of a family in which neurofibromatosis type 1 (NF1) occurred in two of three siblings born to unaffected parents and in one granddaughter. Linkage analysis showed that the two affected siblings and the daughter of one of them shared the same paternal allele, whereas they had inherited different maternal alleles. We detected a disease-causing deletion (c.4773-3622-?_5749+?del) encompassing three NF1 gene exons in affected individuals. This mutation occurred on the paternally derived allele, arguing for a germline mosaicism in the probands' father. Real-time PCR showed that the mutation was present in about 10-17% of the paternal sperms. Current results confirm that germline mosaicism can explain the recurrence of NF1 in offspring of unaffected parents.
authors.affiliation: IRCCS, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bottillo
authors.forename: Isabella
authors.initials: I
authors.lastname: Torrente
authors.forename: Valentina
authors.initials: V
authors.lastname: Lanari
authors.forename: Valentina
authors.initials: V
authors.lastname: Pinna
authors.forename: Sandra
authors.initials: S
authors.lastname: Giustini
authors.forename: Luigina
authors.initials: L
authors.lastname: Divona
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000483:Alleles; D005091:Exons / Q000235:genetics; D005220:Fathers; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009030:Mosaicism; D009456:Neurofibromatosis 1 / Q000235:genetics*; D025542:Neurofibromin 1 / Q000235:genetics*; D010375:Pedigree; D012008:Recurrence; D017384:Sequence Deletion
chemical_list: D025542:Neurofibromin 1