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A clinical and genetic overview of 18 years neurofibromatosis type 1 molecular diagnostics in the Netherlands
Author(s) -
van Minkelen R.,
van Bever Y.,
Kromosoeto J.N.R.,
WithagenHermans C.J.,
Nieuwlaat A.,
Halley D.J.J.,
van den Ouweland A.M.W.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12187
Subject(s) - neurofibromatosis , missense mutation , genetic counseling , medicine , genotype , genetic testing , loss of heterozygosity , genetics , mutation , prenatal diagnosis , medical genetics , pediatrics , biology , pathology , pregnancy , allele , gene , fetus
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.