Jadayel D, Fain P, Upadhyaya M, Ponder M A, Huson S M, Carey J, Fryer A, Mathew C G, Barker D F, Ponder B A
Section of Human Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Nature. 1990 Feb 8;343(6258):558-9. doi: 10.1038/343558a0.
Von Recklinghausen neurofibromatosis (NF-1) is a common autosomal dominant disorder. The estimated new mutation rate (1 x 10(-4] is one of the highest for a human disorder. Here we report that in 12 of 14 families we have analysed, the new mutation is of paternal origin. This result is similar to that recently obtained for retinoblastoma. In other genetic disorders that show a bias towards paternal origin of new mutations, there is a marked increase in the incidence of mutations with paternal age, consistent with the mutations arising from replication errors in mitosis of spermatogonial stem cells. In retinoblastoma and NF-1, however, such paternal age effects are slight or absent. The mechanism or timing of germline mutation could therefore be different in the two cases.
冯·雷克林霍增氏神经纤维瘤病（NF - 1）是一种常见的常染色体显性疾病。估计的新突变率（1×10⁻⁴）是人类疾病中最高的之一。在此我们报告，在我们分析的14个家族中的12个中，新突变来自父方。这一结果与最近在视网膜母细胞瘤中获得的结果相似。在其他显示新突变偏向父方起源的遗传疾病中，随着父龄增加，突变发生率显著上升，这与突变源于精原干细胞有丝分裂中的复制错误一致。然而，在视网膜母细胞瘤和NF - 1中，这种父龄效应轻微或不存在。因此，这两种情况中生殖系突变的机制或时间可能有所不同。
