Ding Fengjuan, Hou Fei, Shan Shan, Zhao Yan, Jin Hua
Department of Prenatal Diagnosis Center, Jinan Maternal and Child Health Hospital Jinan 250001, Shandong, China.
Am J Transl Res. 2024 Jul 15;16(7):2898-2909. doi: 10.62347/IAQV2788. eCollection 2024.
This study aimed to identify the causative genetic variant in a Chinese family with orofacial clefts.
We retrospectively analyzed the clinical information of a family with orofacial clefts. Then, we performed an etiological genetic analysis of the family using whole exome sequencing analysis and Sanger sequencing. We created a hybrid code-shifting mutation cell line (293T-462het) and evaluated its impact on cell proliferation, migration, and apoptosis, as well as E-cadherin and vimentin expression.
Whole exome sequencing revealed a novel heterozygous variant c.1386del (p.A462Pfs*28) in the interferon regulatory transcription factor 6 () gene in a family with orofacial clefts. Sanger sequencing further confirmed that this heterozygous variant was the genetic cause of orofacial clefts in this family. The c.1386del variant of was classified as likely pathogenic. The heterozygous mutation (c.1386del) enhanced cell proliferation and migration while inhibiting cell apoptosis and regulating the expression of E-cadherin and vimentin.
This study identified a novel c.1386del mutation in the gene and explored how this mutation leads to lip and palate defects. Our results provide a solid theoretical foundation for future genetic detection of these orofacial defects.
本研究旨在鉴定一个患有口面部裂隙的中国家庭中的致病基因变异。
我们回顾性分析了一个患有口面部裂隙家庭的临床信息。然后，我们使用全外显子组测序分析和桑格测序对该家庭进行病因学基因分析。我们创建了一个杂合移码突变细胞系（293T - 462het），并评估其对细胞增殖、迁移和凋亡以及E - 钙黏蛋白和波形蛋白表达的影响。
全外显子组测序在一个患有口面部裂隙的家庭中发现了干扰素调节转录因子6（）基因中的一个新的杂合变异c.1386del（p.A462Pfs*28）。桑格测序进一步证实该杂合变异是这个家庭口面部裂隙的遗传病因。的c.1386del变异被分类为可能致病。杂合突变（c.1386del）增强了细胞增殖和迁移，同时抑制细胞凋亡并调节E - 钙黏蛋白和波形蛋白的表达。
本研究鉴定了基因中的一个新的c.1386del突变，并探索了该突变如何导致唇腭裂缺陷。我们的结果为未来这些口面部缺陷的基因检测提供了坚实的理论基础。
