A Novel PAX3 Variant in a Chinese Pedigree with Nonsyndromic Cleft Lip With or Without Palate
A Novel PAX3 Variant in a Chinese Pedigree with Nonsyndromic Cleft Lip With or Without Palate
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中国谱系中非综合征性唇裂（伴腭裂或不伴腭裂）的 PAX3 新型变异体
DOI：
10.1089/gtmb.2021.0111
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发表时间：
2021-12-01
影响因子：
1.4
通讯作者：
Chen, Feng
中科院分区：
文献类型：
--
作者：
Liang, Wei;Huang, Wenbin;Chen, Feng
目的：伴或不伴腭的非综合征性唇裂（NSCL/P）是一种常见的先天性口面部缺陷，与口面部发育的严重破坏有关。本研究旨在鉴定中国 NSCL/P 家系中潜在的潜在基因变异，其中先证者及其父亲受到影响。方法：从参与者的外周静脉血中提取 DNA，对先证者及其父母进行全外显子组测序。结果：经过筛选，发现配对盒基因 3 (PAX3) 错义变异鉴定出（G_p.Thr31Ser">c.92C>G_p.Thr31Ser），并通过桑格测序验证。该变异可能影响PAX3蛋白的转录抑制结构域，在113个无关健康个体或中国公共数据库中均不存在。保守性分析和计算机预测表明，该变异可能在进化上保守且可能有害。此外，有报道称，携带PAX3变异的小鼠表现出因此，PAX3 错义变异 (G_p.Thr31Ser">c.92C>G_p.Thr31Ser) 是该家族中的候选致病变异。 结论：据我们所知，本研究是第一个报告 NSCL/P 家系中的 PAX3 变异的研究。本研究进一步表明 PAX3 可能与 CL/P 病因有关。
Objectives: Nonsyndromic cleft lip with or without palate (NSCL/P) is a common congenital orofacial defect, which is associated with severe disruption of orofacial development. The present study was designed to identify potential underlying gene variants in a Chinese pedigree with NSCL/P, in which the proband and the proband's father were affected.Methods: DNA was extracted from the participants' peripheral venous blood, and whole-exome sequencing was performed on the proband and the proband's parents.Results: After filtering, a paired box gene 3 (PAX3) missense variant (G_p.Thr31Ser">c.92C>G_p.Thr31Ser) was identified, which was verified by Sanger sequencing. This variant, which was not present in 113 unrelated healthy individuals or in a Chinese public database, may affect the transcription inhibition domain of the PAX3 protein. Conservation analysis and in silico predictions suggested that this variant may be evolutionarily conserved and potentially deleterious. In addition, it was reported that mice with PAX3 variants show cleft palates. Thus, the PAX3 missense variant (G_p.Thr31Ser">c.92C>G_p.Thr31Ser) is a candidate causative variant in this family.Conclusions: To the best of our knowledge, the present study is the first to report on a PAX3 variant in a pedigree with NSCL/P. The present study further suggests that PAX3 may be associated with CL/P etiology.