FGFR-associated craniosynostosis syndromes and gastrointestinal defects.
FGFR-associated craniosynostosis syndromes and gastrointestinal defects.
复制标题
DOI：
10.1002/ajmg.a.37862
复制
发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Gong SG
中科院分区：
文献类型：
--
作者：
Hibberd CE;Bowdin S;Arudchelvan Y;Forrest CR;Brakora KA;Marcucio RS;Gong SG
颅缝闭闭是一种相对常见的先天性缺陷，其特征是一条或多条颅缝过早融合。颅缝闭锁综合征的例子包括Crouzon （CS）、Pfeiffer （PS）和Apert （AS）综合征，其临床特征为面中部发育不全、远端增生，在某些情况下还会出现肢体缺陷。成纤维细胞生长因子受体-2的突变包括已知的颅缝闭锁综合征形式的大部分突变。许多fgfr相关颅缝闭锁患者和小鼠突变体的临床报告与胃肠道（GIT）疾病有关，导致fgfr相关颅缝闭锁综合征与GIT畸形之间存在直接联系的假设。我们进行了一项调查，以确定fgfr相关颅缝闭锁综合征患者样本和含有Fgfr2突变（W290R）的CS小鼠模型中的GIT症状。我们发现，与一般人群相比，在fgfr相关颅缝闭锁综合征患者的样本人群中，肠/肠旋转不良（IM）的发生率更高。我们还发现，CS小鼠模型的盲肠移位发生率增加，提示IM。这些发现提示fgfr相关颅缝闭锁综合征与GIT畸形之间存在直接关系。我们的研究可能进一步阐明FGFR突变对不同发育系统的潜在广泛影响。基于对伴有颅缝闭合综合征的儿童GIT畸形的报道和我们的动物模型的证实，任何伴有fgfr2相关颅缝闭合综合征的儿童都应考虑GIT畸形。
Craniosynostosis is a relatively common birth defect characterized by the premature fusion of one or more cranial sutures. Examples of craniosynostosis syndromes include Crouzon (CS), Pfeiffer (PS) and Apert (AS) syndrome, with clinical characteristics such as midface hypoplasia, hypertelorism and in some cases, limb defects. Mutations in Fibroblast Growth Factor Receptor-2 comprise the majority of known mutations in syndromic forms of craniosynostosis. A number of clinical reports of FGFR-associated craniosynostosis patients and mouse mutants have been linked to gastrointestinal tract (GIT) disorders, leading to the hypothesis of a direct link between FGFR-associated craniosynostosis syndromes and GIT malformations. We conducted an investigation to determine GIT symptoms in a sample of FGFR-associated craniosynostosis syndrome patients and a mouse model of CS containing a mutation (W290R) in Fgfr2. We found that, compared to the general population, the incidence of intestinal/bowel malrotation (IM) was present at a higher level in our sample population of patients with FGFR-associated craniosynostosis syndromes. We also showed that the mouse model of CS had an increased incidence of cecal displacement, suggestive of IM. These findings suggest a direct relationship between FGFR-related craniosynostosis syndromes and GIT malformations. Our study may shed further light on the potential widespread impact FGFR mutations on different developmental systems. Based on reports of GIT malformations in children with craniosynostosis syndromes and substantiation with our animal model, GIT malformations should be considered in any child with an FGFR2-associated craniosynostosis syndrome.
登录
查看更多内容
影响因子：
1.6
作者：
Jadico, Suzanne K.;Young, David A.;Young, Terri L.
通讯作者：
Young, Terri L.
影响因子：
2.5
作者：
Adams, Stephen D.;Stanton, Michael P.
通讯作者：
Stanton, Michael P.
DOI：
10.1002/ajmg.1320450616
发表时间：
1993-03-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
BARONE, CM;MARION, R;SHPRINTZEN, RJ
通讯作者：
SHPRINTZEN, RJ
DOI：
10.1002/bdra.23172
发表时间：
2013-09-01
影响因子：
--
作者：
Dab, Sandeep;Sokhi, Ramanpreet;Gong, Siew-Ging
通讯作者：
Gong, Siew-Ging
Pfeiffer综合征FGFR2基因突变谱分析
影响因子：
5.3
作者：
Cornejo-Roldan, LR;Roessler, E;Muenke, M
通讯作者：
Muenke, M