Abstract：
BACKGROUND: Global developmental delay with speech and behavioral abnormalities (OMIM: 619243) is an autosomal dominant disease caused by variants in TNRC6B gene.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：伴有言语和行为异常的全球发育迟缓（OMIM：619243）是由TNRC6B基因变异引起的常染色体显性疾病。
方法：我们回顾并总结了以前报道的TNRC6B基因变异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，并进行了小基因测定来验证影响RNA剪接的同义变体的功能。
结果：患者出现惊厥性癫痫发作和发育迟缓。WES与功能研究相结合，诊断出一名儿童具有TNRC6B基因的同义变异。通过小基因分析和桑格测序，我们证明c.3141G>A变体诱导外显子7跳跃，同义变体是致病性的。
结论：同义变体不改变密码子编码的氨基酸，所以我们通常认为同义变异是良性的，而忽略了它们的致病性。小基因测定是鉴定变异对RNA剪接的影响和鉴定同义变体“良性或致病性”的有价值的工具。我们通过小基因测定表明同义变体是致病性的。WES结合小基因测定为遗传咨询和诊断疾病建立了坚实的基础。
方法：我们回顾并总结了以前报道的TNRC6B基因变异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，并进行了小基因测定来验证影响RNA剪接的同义变体的功能。
结果：患者出现惊厥性癫痫发作和发育迟缓。WES与功能研究相结合，诊断出一名儿童具有TNRC6B基因的同义变异。通过小基因分析和桑格测序，我们证明c.3141G>A变体诱导外显子7跳跃，同义变体是致病性的。
结论：同义变体不改变密码子编码的氨基酸，所以我们通常认为同义变异是良性的，而忽略了它们的致病性。小基因测定是鉴定变异对RNA剪接的影响和鉴定同义变体“良性或致病性”的有价值的工具。我们通过小基因测定表明同义变体是致病性的。WES结合小基因测定为遗传咨询和诊断疾病建立了坚实的基础。
