Exclusive paternal origin of new mutations in Apert syndrome
Exclusive paternal origin of new mutations in Apert syndrome
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DOI：
10.1038/ng0596-48
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发表时间：
1996-05-01
期刊：
影响因子：
30.8
通讯作者：
Wilkie, AOM
中科院分区：
文献类型：
--
作者：
Moloney, DM;Slaney, SF;Wilkie, AOM
阿佩尔综合征是由成纤维细胞生长因子受体 2 (FGFR2) 基因中两种特定核苷酸取代（均为 C-->G 颠换）中的一种或另一种引起的。新突变的频率估计为每 65,000 个活产婴儿中就有 1 个，这意味着这两个位置的种系颠倒率是目前人类基因组中已知最高的。使用扩增阻滞突变系统（ARMS）的新应用，我们确定了 57 个 Apert 家族中新突变的亲本起源：在每种情况下，突变都来自父亲。这确定了先前针对这种疾病提出的新突变的父亲年龄效应的生物学基础。
Apert syndrome results from one or other of two specific nucleotide substitutions, both C-->G transversions, in the fibroblast growth factor receptor 2 (FGFR2) gene. The frequency of new mutations, estimated as 1 per 65,000 live births, implies germline transversion rates at these two positions are currently the highest known in the human genome. Using a novel application of the amplification refractory mutation system (ARMS), we have determined the parental origin of the new mutation in 57 Apert families: in every case, the mutation arose from the father. This identifies the biological basis of the paternal age effect for new mutations previously suggested for this disorder.