神经纤维瘤病
错义突变
遗传咨询
医学
基因型
遗传学
基因检测
杂合子丢失
突变
产前诊断
医学遗传学
儿科
内科学
病理
生物
怀孕
等位基因
基因
胎儿
作者
Rick van Minkelen,Yolande van Bever,Joan N. R. Kromosoeto,Caroline Withagen-Hermans,Anja Nieuwlaat,Dicky Halley,A.M.W. van den Ouweland
摘要
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.
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