2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Pathogenic Variants Detected in High Homology Segments of the <em>PMS2 </em>Gene in a Brazilian Sample.

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This study aimed to confirm the presence of pathogenic or likely pathogenic (P/LP) variants in the PMS2 gene, which is associated with Lynch Syndrome (LS), a hereditary cancer syndrome. The PMS2 gene has high homology with its pseudogene, PMS2CL, which makes variant detection challenging. The study analyzed 76 samples from a Brazilian laboratory using next-generation sequencing (NGS) and confirmed the detected variants using the gold standard method, Long-Range PCR.<br /><br />The results showed that 4 out of 76 samples (5%) had confirmed pathogenic variants in the regions of high homology with the PMS2 gene. These variants were NM_000535.7:c.1239dup and NM_000535.7:c.2192_2196del. The other 71 samples did not confirm the presence of the variant. The study emphasizes the importance of confirming NGS results with Long-Range PCR to avoid misdiagnoses and ensure appropriate clinical management of patients with LS.<br /><br />The methodology involved DNA extraction using QIASymphony and DNA Mini Kit, PCR amplification, agarose gel analysis, amplicon purification, library preparation, Sanger sequencing, and data analysis. The variants were analyzed using CLC software and specific primers were used for amplification of the PMS2 gene.<br /><br />In conclusion, confirming NGS results with Long-Range PCR is crucial for accurately diagnosing and managing Lynch Syndrome. The study highlights the importance of evaluating the PMS2 gene, which is often neglected due to methodological difficulties in reporting reliable variants. By confirming the presence of pathogenic variants in the high homology regions, this study provides more reliable results for clinical management.<br /><br />The study contributes to the understanding of the molecular genetics of Lynch Syndrome and provides a validated methodology for variant detection in the PMS2 gene. This research was conducted in Brazil and involved samples from Grupo Fleury Laboratory.

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Co-Author - THALITTA HA. LIMA, PhD; Co-Author - Daniele Paixão, MD, PhD; Presenting Author - Larissa S. Bueno, MD; Co-Author - Rafaela F. Sousa, MSc; Co-Author - Juliana P. Carnavalli, MSc; Co-Author - Maria Júlia B. Bezerra, PhD; Co-Author - Flavio S. Bitencourt, PhD; Co-Author - Maria Claudia S. Luciano, PhD; Co-Author - Rosane O. Sant'ana, PhD; Co-Author - Caroline M. Moreira, MSc; Co-Author - Wagner R. Baratela, MD; Co-Author - Miguel Mitne-Neto, PhD;

Meta Tag

Cancer Syndromes

Counseling

Genetic Testing

Genome sequencing

Genomic Methodologies

Methodology

Oncogenesis

Risk Assessment

Sequencing

Co-Author THALITTA HA. LIMA, PhD

Co-Author Daniele Paixão, MD, PhD

Co-Author Rafaela F. Sousa, MSc

Co-Author Juliana P. Carnavalli, MSc

Co-Author Maria Júlia B. Bezerra, PhD

Co-Author Flavio S. Bitencourt, PhD

Co-Author Maria Claudia S. Luciano, PhD

Co-Author Rosane O. Sant'ana, PhD

Co-Author Caroline M. Moreira, MSc

Co-Author Wagner R. Baratela, MD

Co-Author Miguel Mitne-Neto, PhD

Presenting Author Larissa S. Bueno, MD

Keywords

PMS2 gene

pathogenic variants

Lynch Syndrome

hereditary cancer syndrome

next-generation sequencing

Long-Range PCR

variant detection

homology regions

clinical management

molecular genetics