title: Clinical presentations of 23 half-siblings from a mosaic neurofibromatosis type 1 sperm donor.
abstract: The Danish sperm donor number 7042 has fathered several offspring with neurofibromatosis type 1 (NF1) worldwide. NF1 is caused by loss-of-function mutations in the NF1 gene and more than 1000 NF1 mutations are identified. Analysis of the donor sperm demonstrated gonosomal mosaicism with an intragenic deletion involving exons 15-29 in the NF1 gene. At the two Danish reference centres for NF1 patients, we evaluated 23 half-siblings from the donor. Nine were diagnosed with NF1. The severity grade of NF1 progressed from minimal to mild/moderate within 3 years of follow-up. The NF1 phenotype shows great variability in intra- and inter-family expressivity and to date only two NF1 genotype-phenotype correlations have been established. This rare possibility of a long-term follow-up of a cohort of half-siblings with NF1 makes further studies including phenotypic variability and search for modifier genes possible. To achieve this goal, we have initiated The International Donor 7042 NF1 Offspring Registry. Research facilitated via this registry may reveal important new knowledge of clinical characteristics and prognostics for the specific NF1 genotype and thereby contribute to future individualised targeted clinical follow-up and treatment.
authors: Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors: C
authors: C
authors: Ejerskov
authors: Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors: S
authors: S
authors: Farholt
authors: Centre for Rare Diseases, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
authors: F
authors: F
authors: Skovby
authors: Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
authors: E M
authors: EM
authors: Vestergaard
authors: Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors: A
authors: A
authors: Haagerup
mesh_terms: D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D009030:Mosaicism; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism; D025542:Neurofibromin 1 / Q000235:genetics; D010375:Pedigree; D012661:Semen; D017384:Sequence Deletion; D035781:Siblings; D014019:Tissue Donors
chemical_list: D025542:Neurofibromin 1
keywords: 17q11.2; genotype-phenotype correlation; gonosomal mosaicism; neurofibromatosis type 1