Novel SCN5A and GPD1L Variants Identified in Two Unrelated Han-Chinese Patients With Clinically Suspected Brugada Syndrome

Abstract

Brugada syndrome (BrS) is a complexly genetically patterned, rare, malignant, life-threatening arrhythmia disorder. It is autosomal dominant in most cases and characterized by identifiable electrocardiographic patterns, recurrent syncope, nocturnal agonal respiration, and other symptoms, including sudden cardiac death. Over the last 2 decades, a great number of variants have been identified in more than 36 pathogenic or susceptibility genes associated with BrS. The present study used the combined method of whole exome sequencing and Sanger sequencing to identify pathogenic variants in two unrelated Han-Chinese patients with clinically suspected BrS. Minigene splicing assay was used to evaluate the effects of the splicing variant. A novel heterozygous splicing variant c.2437-2A>C in the sodium voltage-gated channel alpha subunit 5 gene (SCN5A) and a novel heterozygous missense variant c.161A>T [p.(Asp54Val)] in the glycerol-3-phosphate dehydrogenase 1 like gene (GPD1L) were identified in these two patients with BrS-1 and possible BrS-2, respectively. Minigene splicing assay indicated the deletion of 15 and 141 nucleotides in exon 16, resulting in critical amino acid deletions. These findings expand the variant spectrum of SCN5A and GPD1L, which can be beneficial to genetic counseling and prenatal diagnosis.

Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2

“…Given that the proband is presented with typical symptoms of CLN2, which follows an autosomal recessive inheritance pattern ( Goebel and Sharp, 1998 ), we speculated that the variant c.230-3C>G might also be pathogenic. To further clarify the pathological significance of the c.230-3C>G variant, we determined the impact of the variant on transcript splicing using the Splicing Reporter Minigene assay ( Hartikainen et al, 1999 ; Yuan et al, 2021 ). The RT-PCR products were analyzed by electrophoresis, and the results showed that the length of the PCR product was shortened in the MT construct ( Figure 3A ), indicating that aberrant splicing occurred.…”

Development and validation of a metabolic gene signature for predicting the overall survival of patients in lung adenocarcinoma with lymph node metastasis

“…Knockdown of POLR3G resulted in reduced clonal formation of lung cancer cells and increased chemosensitivity of lung cancer cells to paclitaxel (Park et al 2023). GPD1L, which is located on chromosome 3p22.3 (Shrestha et al 2018), catalyze the conversion of sn-glycerol 3-phosphate to glycerone phosphate (Yuan et al 2021) and was found to be involved in more than one type of tumor. For example, Liu et The current study had some limitations.…”

The TSC2 c.2742+5G>A variant causes variable splicing changes and clinical manifestations in a family with tuberous sclerosis complex

“…The wild-type and mutant DNA sequences spanning TSC2 gene exons 23–27 and introns 23–26 were amplified from the gDNA of the patient II:2 and introduced into the pMini-SP vector (Beijing Hitrobio Biotechnology Co., Ltd., Beijing, China) (Yuan et al, 2021 ). Human embryonic kidney (HEK) 293T cells were prepared in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (HyClone, Logan, Utah, USA) at 37°C and 5% CO 2 .…”