Graduate College of Tianjin Medical University, Tianjin, 300100, China.
Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin, 300134, China.
Mol Biol Rep. 2024 Aug 8;51(1):899. doi: 10.1007/s11033-024-09835-5.
Global developmental delay with speech and behavioral abnormalities (OMIM: 619243) is an autosomal dominant disease caused by variants in TNRC6B gene.
We reviewed and summarized clinical manifestations and genotypes in patients previously reported with TNRC6B gene variants. We used several prediction tools to predict pathogenicity and performed minigene assays to verify the function of the synonymous variant affecting RNA splicing.
The patient presented with convulsive seizures and developmental delay. WES combined with functional studies diagnosed a child with a synonymous variant in TNRC6B gene. Through minigene assay and Sanger sequencing, we demonstrated that c.3141G > A variant induced exon 7 skipping and the synonymous variant was pathogenic.
Synonymous variants do not change the amino acids encoded by the codon, so we usually consider synonymous variants to be benign and ignore their pathogenicity. Minigene assay is a valuable tool to identify the effect of variation on RNA splicing and identify synonymous variants' benign or pathogenic. We showed that the synonymous variant was pathogenic by minigene assay. WES combined with minigene assay establishes a robust basis for genetic counseling and diagnosing diseases.
伴有言语和行为异常的全球发育迟缓（OMIM：619243）是一种常染色体显性疾病，由 TNRC6B 基因突变引起。
我们回顾并总结了先前报道的 TNRC6B 基因突变患者的临床表现和基因型。我们使用了几种预测工具来预测致病性，并进行了小基因检测以验证影响 RNA 剪接的同义变异的功能。
患者表现为癫痫发作和发育迟缓。WES 结合功能研究诊断出一名儿童携带 TNRC6B 基因的同义变异。通过小基因检测和 Sanger 测序，我们证明了 c.3141G>A 变异导致外显子 7 跳跃，该同义变异具有致病性。
同义变异不会改变密码子编码的氨基酸，因此我们通常认为同义变异是良性的，忽略其致病性。小基因检测是一种识别变异对 RNA 剪接影响并鉴定同义变异良性或致病性的有效工具。我们通过小基因检测证明了该同义变异具有致病性。WES 结合小基因检测为遗传咨询和疾病诊断奠定了坚实的基础。
