Clustering of FGFR2 gene mutations in patients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses)
Clustering of FGFR2 gene mutations in patients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses)
复制标题
Pfeiffer 和 Crouzon 综合征（FGFR2 相关性颅缝早闭）患者 FGFR2 基因突变的聚集
DOI：
10.1159/000056833
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Mueller, CR
中科院分区：
文献类型：
--
作者：
Kress, W;Collmann, H;Mueller, CR
对36名患有Crouzon和Pfeiffer型颅缝早闭综合征的无关德国患者进行了FGFR突变分析。在15名Crouzon综合征患者和5名Pfeiffer综合征患者中发现了FGFR2的突变，而其余患者即使在筛选FGFR1、FGER3和twist的相关部分后也没有发现序列变化。FGFR2基因突变集中在两个关键的半胱氨酸残基278和342，在30例患者中有18例(60%)受累。因此，这两个突变热点是有效突变筛选策略的主要目标。突变谱与两个综合征重叠，因此反映了在两个患者组中观察到的表型相似性。在21个家系中，通过分析父母和亲属可以追踪突变的来源。11个突变从头开始，表明FGFR2的突变率很高。在10个家族性病例中，家系内的临床表现差异很大，但两个综合征都是真的，即在Crouzon综合征家族中从未观察到Pfeiffer综合征表型，反之亦然。版权所有(C)2001 S.Karger AG，巴塞尔。
A cohort of 36 unrelated German patients with craniosynostosis syndromes of the Crouzon and Pfeiffer type were analyzed for FGFR mutations. Mutations in FGFR2 were identified in 15 Crouzon and 5 Pfeiffer syndrome patients, whereas no sequence alterations were found in the remaining patients, even after screening of the relevant parts of FGFR1, FGER3, and TWIST. Mutations in FGFR2 clustered at two critical cysteine residues, 278 and 342, which were involved in 18 of 30 cases (60%). These two mutational hot spots, therefore, are prime targets for an efficient mutation-screening strategy. The spectrum of mutations overlapped the two syndromes and thus reflected the phenotypic similarities observed in both patient groups. In 21 families, the origin of the mutation could be traced by analyzing parents and relatives. Eleven mutations arose de novo, indicating a high mutation rate for FGFR2. In the 10 familial cases, the clinical presentation varied considerably within the pedigree, but both syndromes "bred true," i.e., a Pfeiffer syndrome phenotype was never observed in a Crouzon syndrome family and vice versa. Copyright (C) 2001 S. Karger AG, Basel.