title: A clinical and genetic overview of 18 years neurofibromatosis type 1 molecular diagnostics in the Netherlands.
abstract: NF1 mutations are the underlying cause of neurofibromatosis type 1 (NF1), a neuro-cardio-facio-cutaneous syndrome (NCFC). Because of the clinical overlap between NCFCs, genetic analysis of NF1 is necessary to confirm a clinical diagnosis NF1. This report describes the clinical and genetic findings of 18 years of NF1 molecular diagnostics in the Netherlands. A pathogenic mutation was found in 59.3% (1178/1985) of the index patients, mostly de novo (73.8%). The majority of the index patients (64.3%) fulfilled the National Institute of Health NF1 criteria, a pathogenic mutation was found in 80.9% of these patients. Seventy-four percent of the index patients with an NF1 pathogenic mutation and not fulfilling the NF1 criteria is <12 years, in agreement with the fact that some NF1 symptoms appear after puberty. Genotype-phenotype correlations were studied for 527 index patients. NF1 patients with a type 1 microdeletion have a sixfold higher risk of special education vs NF1 patients with an intragenic mutation. No evidently milder NF1 phenotype for patients with a missense mutation was observed. Forty-six prenatal analyses were performed in 28 (2.4%) families, of which 29 (63%) showed heterozygosity for the familial pathogenic mutation. This indicates that there is a need for prenatal NF1 testing.
authors: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: R
authors: R
authors: van Minkelen
authors: Y
authors: Y
authors: van Bever
authors: J N R
authors: JN
authors: Kromosoeto
authors: C J
authors: CJ
authors: Withagen-Hermans
authors: A
authors: A
authors: Nieuwlaat
authors: D J J
authors: DJ
authors: Halley
authors: A M W
authors: AM
authors: van den Ouweland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D009456:Neurofibromatosis 1 / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D025542:Neurofibromin 1 / Q000235:genetics; D010375:Pedigree; D055815:Young Adult
chemical_list: D025542:Neurofibromin 1
keywords: (prenatal) molecular diagnostics; clinical; genetic; neurofibromatosis type 1; the Netherlands