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The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

Abstract Background Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by skin fragility leading to trauma‐induced subepidermal blisters and healing with scarring. DEB is caused by mutations in COL7A1, the gene encoding for type VII collagen (COLVII). The DEB inheritance trait is divided into dominant dystrophic epidermolysis bullosa (DDEB) and recessive dystrophic epidermolysis bullosa (RDEB). Methods Whole‐exome sequencing (WES) was performed for identifying mutations in six affected individuals of five Vietnamese families. Results Three novel variants in total of eight variants were found in five families. The first novel variant causing glycine substitution (c.8279G>A, p.G2760E), the remaining two novel variants resulted in splice site affecting (c.4518+2delT and c.5821‐2A>G). Functional analysis indicated that the splice site at c.4518+2delT resulted in a skipping of exon 43, leading to an in‐frame deletion of 12 amino acids. Conclusion Our finding expands the spectrum of COL7A1 mutations and reports altered splicing at c.4518+2delT during the processing of the pre‐mRNA. This study provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes of EB patients.

Abstract Background Brugada syndrome (BrS) is a rare genetic disease that causes sudden cardiac death (SCD) and arrhythmia. SCN5A pathogenic variants (about 30% of diagnosed patients) are responsible for BrS. Aims Lack of knowledge regarding molecular characteristics and the correlation between genotype and phenotype interfere with the risk stratification and finding the optimal treatment in Vietnam. Therefore, we identified SCN5A variants and evaluated the genotype–phenotype correlation of BrS on 117 Vietnamese probands. Materials and Methods The clinical characteristics and blood samples of BrS patients were collected. To determine SCN5A variants, Sanger sequencing was conducted, and subsequently, these variants were analyzed by bioinformatic tools. Results In this cohort, the overall rate of detected variants in SCN5A was 25.6%, which could include both pathogenic and benign variants. In genetic testing, 21 SCN5A variants were identified, including eight novels and 15 published variants. Multiple bioinformatic tools were used to predict variant effect with c.551A>G, c.1890+14G>A, c.3338C>T, c.3578G>A, and c.5484C>T as benign, while other variants were predicted as disease‐causing. The family history of SCD (risk ratio [RR] = 4.324, 95% CI: 2.290–8.269, p

Microdeletions of Y chromosomes frequently occur in 3 subregions of the AZF, namely, AZFa, AZFb, and AZFc, with 6 basic STS marker sequences, which are sY84, sY86 (AZFa), sY127, sY134 (AZFb), and sY254, sY255 (AZFc). According to EAA/EMNQ guidelines, 11 additional AZFabc marker sequences should be used to determine the extent of the microdeletion in the AZF region of infertile men, which is known as 11 extended STSs. By applying mPCR, the authors develop an optimal detection procedure for the 6 basic STS and 11 extended STS using 3 multiplex PCR reactions. The first multiplex PCR reaction includes 6 basic STS plus the 2 control sequences sex-determining region Y (SRY) and zinc finger protein X/Y-linked (ZFX/Y). The second multiplex PCR reaction includes the 6 extended STS sY88, sY1182, sY105, sY121, sY1191, and sY1291 and the 2 control sequences SRY and ZFX/Y. The third multiplex PCR reaction includes the 5 extended STS sY153, sY160, sY82, sY143, and sY83 and the 2 control sequences SRY and ZFX/Y. Six basic primer sequences and eleven extended primer sequences are redesigned to simultaneously pair and amplify STS in the same multiplex reaction: set of 8 primers for 6 basic STS: 6 basic STS + 2 (SRY, ZFX/Y), 8 extension primers set E1: 6 extended STS + 2 (SRY, ZFX/Y), and 7 extension primers set E2: 5 extended STS + 2 (SRY, ZFX/Y). We successfully designed primer pairs with high specificity and stability and successfully amplified 6 basic STS and 11 extended STS, which ensures that the STSs have the correct sequence as recommended by EAA/EMQN and are consistent with the NCBI gene bank. This study has successfully developed a procedure to simultaneously detect 17 STSs, including 6 basic STSs and 11 extended STSs in the AZF region using 3 multiplex PCR reactions.