A novel FZD6 mutation revealed the cause of cleft lip and/or palate in a Chinese family
A novel FZD6 mutation revealed the cause of cleft lip and/or palate in a Chinese family
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一种新的 FZD6 突变揭示了一个中国家庭唇裂和/或腭裂的原因
DOI：
10.1016/j.gendis.2019.12.003
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发表时间：
2019-12
期刊：
影响因子：
--
通讯作者：
Feng Chen
中科院分区：
文献类型：
--
作者：
Jieni Zhang;Huaxiang Zhao;Wenbin Huang;Fengqi Song;Wenjie Zhong;Mengqi Zhang;Yunfan Zhang;Zhibo Zhou;Jiuxiang Lin;Feng Chen
唇腭裂（CL/P）是一种常见的颅面出生缺陷，其病因复杂。在我们的研究中，我们的目的是发现潜在的致病基因变异，在中国家庭诊断为非综合征CL/P（NSCL/P）。先证者及其父母的血液样本采用全外显子测序法进行检测。采用孟德尔遗传模式、等位基因频率、变异位点、功能分析和文献检索等方法对突变进行筛选。此外，通过桑格测序确认候选者。同时，我们还对保守性分析和蛋白质同源性模拟进行了探索。结果，在预测p.Met1的卷曲蛋白6（FZD 6）基因中检测到起始丢失突变c.1A > GAtg/Gtg。这种变异以前没有报道过，预计是有害的。该改变导致FZD 6蛋白的两个进化上保守的起始氨基酸缺失。此外，根据同源模型的结果，突变蛋白的特定结构发生了明显的变化。FZD 6（NM_001164616）的c.1A > GAtg/Gtg可能是该家系非综合征型CL/P的遗传病因。此外，这一发现提供了新的病因学信息，补充了FZD 6是CL/P的强潜在基因的证据。
Cleft lip and/or palate (CL/P) is a most common craniofacial birth defect which has multifactorial etiology. In our study, we aimed to discover the underlying etiological gene variation in a Chinese family diagnosed as non-syndromic CL/P (NSCL/P). The blood sample of the proband and her parents were detected by whole exome sequencing. The Mendelian inheritance pattern, allele frequency, variation location, function analysis and literature search were applied to filtrate and screen the mutation. Besides, the candidates were confirmed by Sanger sequencing. We meanwhile explored the conservative analysis and protein homology simulation. As a result, a start-lost mutation c.1A > GAtg/Gtg in the Frizzled-6 (FZD6) gene predicting p.Met1 was detected. The variation has not been reported before and was predicted to be harmful. The alteration caused missing of two starting amino acids that are evolutionarily conserved for FZD6 protein. Moreover, the specific structure of the mutant protein obviously changed according to the results of the homologous model. In conclusion, the results suggest c.1A > GAtg/Gtg in theFZD6(NM_001164616) might be the genetic etiology for non-syndromic CL/P in this pedigree. Furthermore, this finding provided new etiologic information, supplementing the evidence thatFZD6is a strong potential gene for CL/P.
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DOI：
10.1016/j.gep.2009.07.003
发表时间：
2009-10
期刊：
Gene expression patterns : GEP
影响因子：
--
作者：
Sisson BE;Topczewski J
通讯作者：
Topczewski J
DOI：
10.1007/3-540-30020-1
发表时间：
2006
期刊：
--
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1002/bdra.20302
发表时间：
2006-08-01
影响因子：
--
作者：
Juriloff, Diana M.;Harris, Muriel J.;Lidral, Andrew C.
通讯作者：
Lidral, Andrew C.
影响因子：
3.8
作者：
Huaxiang Zhao;Wenjie Zhong;Chuntao Leng;Jieni Zhang;Mengqi Zhang;Wen-Zhi Huang;Yunfan Zhang;
通讯作者：
Huaxiang Zhao;Wenjie Zhong;Chuntao Leng;Jieni Zhang;Mengqi Zhang;Wen-Zhi Huang;Yunfan Zhang;
影响因子：
3.5
作者：
Tian, Hua;Feng, Jifan;Chai, Yang
通讯作者：
Chai, Yang