NOVEL FGFR2 MUTATIONS IN CROUZON AND JACKSON-WEISS SYNDROMES SHOW ALLELIC HETEROGENEITY AND PHENOTYPIC VARIABILITY
NOVEL FGFR2 MUTATIONS IN CROUZON AND JACKSON-WEISS SYNDROMES SHOW ALLELIC HETEROGENEITY AND PHENOTYPIC VARIABILITY
复制标题
Crouzon 和 Jackson-Weiss 综合征中的新 FGFR2 突变显示等位基因异质性和表型变异性
DOI：
10.1093/hmg/4.7.1229
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发表时间：
1995-07-01
影响因子：
3.5
通讯作者：
JABS, EW
中科院分区：
文献类型：
--
作者：
PARK, WJ;MEYERS, GA;JABS, EW
据报道，成纤维细胞生长因子受体2基因（FGFR2）的外显子IIIa（外显子U或7）或IIIc（外显子B或9）发生了几种颅缝闭锁疾病，FGFR2突变的情况包括两种常染色体显性综合征，Crouzon和Jackson-Weiss。本研究对24例Crouzon和1例Jackson-Weiss综合征患者进行了直接测序，筛选了2个外显子的突变，28%（7/25）的患者检测到突变，发现5个不同的突变，包括2个新的（W290G, C342W）和2个既往报道的复发性突变（A344A, S354C）， 1个新的Jackson-Weiss综合征突变（C342R）。W290G突变在IIIa外显子中被发现，这是FGFR2， BEK（主要表达于原始骨骼）和KGFR（优先表达于上皮细胞）的可选剪接形式所共有的，在两个受影响的突变家族成员中存在上皮来源的肛门和/或外耳异常的非典型Crouzon综合征特征，这种表型可能反映了突变的BEK和KGFR的表达。此外，Jackson-Weiss综合征突变，C342R，外显子IIIc先前在其他颅缝闭合综合征，Crouzon和Pfeiffer中也观察到。这些结果强调了这些条件的等位基因异质性和FGFR2突变的表型后果的复杂性。
Mutations have been reported for several craniosynostotic disorders in exon IIIa (exon U or 7) or IIIc (exon B or 9) of the fibroblast growth factor receptor 2 gene (FGFR2), Among the conditions with FGFR2 mutations are two autosomal dominant syndromes, Crouzon and Jackson-Weiss. In this study, 24 Crouzon and one Jackson-Weiss syndrome patients were screened for mutations in the two exons by direct sequencing, and mutations were detected in 28% (7/25) of all cases, Five different mutations were found including two novel (W290G, C342W) and two previously reported, recurrent mutations for Crouzon syndrome (A344A, S354C), and one new mutation for Jackson-Weiss syndrome (C342R), The W290G mutation was found in exon IIIa which is common to both alternatively spliced forms of FGFR2, BEK (expressed predominantly in primordial bones) and KGFR (expressed preferentially in epithelia), Atypical Crouzon syndrome features of epithelial-derived anal and/or external ear anomalies were present in the two affected family members with the mutation, This phenotype possibly reflects the expression of both mutant BEK and KGFR, In addition, the Jackson-Weiss syndrome mutation, C342R, in exon IIIc was observed previously in other craniosynostotic syndromes, Crouzon and Pfeiffer. These results underscore the allelic heterogeneity of these conditions and the complexity of the phenotypic consequences of FGFR2 mutations.