Molecular analysis of FGFR 2 and associated clinical observations in two Chinese families with Crouzon syndrome.
Molecular analysis of FGFR 2 and associated clinical observations in two Chinese families with Crouzon syndrome.
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DOI：
10.3892/mmr.2016.5497
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发表时间：
2016-09
影响因子：
3.4
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Lin Y;Gao H;Ai S;Eswarakumar JV;Li T;Liu B;Jiang H;Liu Y;Liu X;Li Y;Ni Y;Chen J;Lin Z;Liang X;Jin C;Huang X;Lu L;Liu Y
克鲁宗综合征是一种显性遗传性疾病，也是最常见的颅缝早闭综合征，由成纤维细胞生长因子受体 2 (FGFR 2) 基因突变引起，其特征为颅缝早闭、眼眶浅、眼球突出、面中部发育不全和弯曲的喙状鼻子。本研究的目的是调查两个中国克鲁宗综合征家系的成纤维细胞生长因子受体 2 (FGFR 2) 基因，并表征相关的临床特征。两个家庭接受了完整的眼科检查，两个家庭的3名患者被诊断为克鲁宗综合征。基因组 DNA 是从外周血样本的白细胞中提取的，这些样本是从同一人群的家庭成员和 200 名无关对照受试者中采集的。使用聚合酶链式反应分析扩增 FGFR 2 基因的外显子 8 和 10，并直接测序。进行眼科检查，包括最佳矫正视力、裂隙灯检查、眼底检查和计算机断层扫描，以及体检以排除全身性疾病。这些患者患有浅眼眶和眼球突出，伴有中面部发育不全、颅缝早闭、斜视或视乳头水肿，但手足临床正常。在受影响的个体中发现了外显子 8 中的杂合 FGFR 2 错义突变 c.811-812insGAG (p.273insGlu)，但在未受影响的家庭成员或家庭 1 中的正常对照个体中未发现。在家庭 2 中，外显子中存在另一个杂合 FGFR 2 错义突变 c.842A>G（P.Tyr281Cys 或 Y281C）在受影响的男孩和他的母亲中发现了 8，但在未受影响的家庭成员或正常对照个体中未发现。尽管 FGFR 2 基因突变和多态性已在不同种族群体中得到报道，特别是在骨学领域，但据我们所知，本研究首次报告在中国克鲁松综合征患者中鉴定出两种新的 FGFR 2 基因突变。
Crouzon syndrome, a dominantly inherited disorder and the most common type of craniosynostosis syndrome, is caused by mutations in the fibroblast growth factor receptor 2 (FGFR 2) gene, and characterized by craniosynostosis, shallow orbits, ocular proptosis, midface hypoplasia and a curved, beak-like nose. The purpose of the present study was to investigate the fibroblast growth factor receptor 2 (FGFR 2) gene in two Chinese families with Crouzon syndrome and to characterize the associated clinical features. Two families underwent complete ophthalmic examination, and three patients in two families were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood samples, which were collected from the family members and 200 unrelated control subjects from the same population. Exons 8 and 10 of the FGFR 2 gene were amplified using polymerase chain reaction analysis and were directly sequenced. Ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination and Computerized Tomography scans, and physical examinations were performed to exclude systemic diseases. These patients were affected with shallow orbits and ocular proptosis, accompanied by midface hypoplasia, craniosynostosis, strabismus or papilloedema, with clinically normal hands and feet. A heterozygous FGFR 2 missense mutation, c.811-812insGAG (p.273insGlu) in exon 8 was identified in the affected individual, but not in the unaffected family members or the normal control individuals in family 1. In family 2, another heterozygous FGFR 2 missense mutation, c.842A>G (P.Tyr281Cys or Y281C), in exon 8 was identified in the affected boy and his mother, but not in the unaffected family members or the normal control individuals. Although FGFR 2 gene mutations and polymorphisms have been reported in various ethnic groups, particularly in the area of osteology, the present study reported for the first time, to the best of our knowledge, the identification of two novel FGFR 2 gene mutations in Chinese patients with Crouzon syndrome.