CROUZON SYNDROME - MUTATIONS IN 2 SPLICEOFORMS OF FGFR2 AND A COMMON POINT MUTATION SHARED WITH JACKSON-WEISS SYNDROME
CROUZON SYNDROME - MUTATIONS IN 2 SPLICEOFORMS OF FGFR2 AND A COMMON POINT MUTATION SHARED WITH JACKSON-WEISS SYNDROME
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DOI：
10.1093/hmg/4.8.1387
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发表时间：
1995-08-01
影响因子：
3.5
通讯作者：
EHRLICH, GD
中科院分区：
文献类型：
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作者：
GORRY, MC;PRESTON, RA;EHRLICH, GD
成纤维细胞生长因子受体2（FGFR 2）基因的显性突变最近被确定为四种表型不同的颅缝早闭综合征的原因，包括Crouzon、Jackson-Weiss、Pfeiffer和Apert综合征。这些数据表明颅缝早闭综合征的遗传学比从其简单的常染色体显性遗传模式所预期的更复杂。FGFR 2基因的相同突变已被报道引起Pfeiffer和Crouzon综合征表型，我们现在报告在一个患有Crouzon综合征的家族中发现FGFR 2基因外显子IIIc突变（C1043至G; Ala 344 Gly）与先前与Jackson-Weiss综合征相关的突变相同，我们还报告了在一个Crouzon家系中发现的外显子IIIu的3'端突变（以前称为外显子5、外显子7或外显子U）（A878至C; Gln 289 Pro），其编码FGFR 2蛋白的Ig样III结构域的氨基末端部分。该外显子对于FGFR 2和FGFR 2基因的KGFR剪接体是共同的，与所有先前报道的仅在FGFR 2剪接型中发现的Crouzon突变不同。这些研究结果揭示了这些颅缝早闭综合征的分子遗传学的进一步意想不到的复杂性，这些数据表明，FGFR 2本身（外显子IIIc外）或其他基因的第二位点突变可能决定颅缝早闭综合征表型的特定方面。
Dominant mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been recently identified as causes of four phenotypically distinct craniosynostosis syndromes, including Crouzon, Jackson-Weiss, Pfeiffer, and Apert syndromes, These data suggest that the genetics of the craniosynostosis syndromes is more complex than would be expected from their simple autosomal-dominant inheritance pattern. Identical mutations in the FGFR2 gene have been reported to cause both Pfeiffer and Crouzon syndrome phenotypes, We now report the finding of a mutation in exon IIIc of the FGFR2 gene in a kindred affected with Crouzon syndrome (C1043 to G; Ala344Gly) that is identical to the mutation previously associated with Jackson-Weiss syndrome, We also report finding in a Crouzon kindred a mutation in the 3' end of exon IIIu (formerly referred to as exon 5, exon 7, or exon U) (A878 to C; Gln289Pro) which encodes the amino terminal portion of the Ig-like III domain of the FGFR2 protein, This exon is common to both the FGFR2 and the KGFR spliceoforms of the FGFR2 gene, unlike all previously reported Crouzon mutations, which have been found only in the FGFR2 spliceoform. These findings reveal further unexpected complexity in the molecular genetics of these craniosynostosis syndromes, The data implies that second-site mutations in FGFR2 itself (outside of exon IIIc) or in other genes may determine specific aspects of the phenotypes of craniosynostosis syndromes.