Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion
Lynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It is associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed a precancero...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5970 |
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| author | Antonio Nolano Giovanni Battista Rossi Valentina D’Angelo Raffaella Liccardo Marina De Rosa Paola Izzo Francesca Duraturo |
| author_facet | Antonio Nolano Giovanni Battista Rossi Valentina D’Angelo Raffaella Liccardo Marina De Rosa Paola Izzo Francesca Duraturo |
| author_sort | Antonio Nolano |
| collection | DOAJ |
| description | Lynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It is associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed a precancerous colonic lesion and had a clinical suspicion of LS. The proband was found to have a somatic MSI-H status. Analysis of the coding sequences and flanking introns of the MLH1 and MSH2 genes by Sanger sequencing led to the identification of the variant of uncertain significance, namely, c.589-9_589-6delGTTT in the MLH1 gene. Further investigation revealed that this variant was likely pathogenetic. Subsequent next-generation sequencing panel analysis revealed the presence of two variants of uncertain significance in the ATM gene. We conclude that the phenotype of our index case is likely the result of a synergistic effect of these identified variants. Future studies will allow us to understand how risk alleles in different colorectal-cancer-prone genes interact with each other to increase an individual’s risk of developing cancer. |
| first_indexed | 2024-03-11T06:23:40Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:23:40Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-05884fb15f4c47ac9c0938428d56c91b2023-11-17T11:41:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246597010.3390/ijms24065970Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic LesionAntonio Nolano0Giovanni Battista Rossi1Valentina D’Angelo2Raffaella Liccardo3Marina De Rosa4Paola Izzo5Francesca Duraturo6Department of Molecular Medicine and Medical Biotechnologies and CEINGE Advanced Biotechnologies Scarl, “Francesco Salvatore” Napoli, University of Naples Federico II, 80131 Naples, ItalyEndoscopy Unit, Istituto Nazionale Tumori–IRCCS–Fondazione G. Pascale, Via Mariano Semola, 80131 Naples, ItalyEndoscopy Unit, Istituto Nazionale Tumori–IRCCS–Fondazione G. Pascale, Via Mariano Semola, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies and CEINGE Advanced Biotechnologies Scarl, “Francesco Salvatore” Napoli, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies and CEINGE Advanced Biotechnologies Scarl, “Francesco Salvatore” Napoli, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies and CEINGE Advanced Biotechnologies Scarl, “Francesco Salvatore” Napoli, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnologies and CEINGE Advanced Biotechnologies Scarl, “Francesco Salvatore” Napoli, University of Naples Federico II, 80131 Naples, ItalyLynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It is associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed a precancerous colonic lesion and had a clinical suspicion of LS. The proband was found to have a somatic MSI-H status. Analysis of the coding sequences and flanking introns of the MLH1 and MSH2 genes by Sanger sequencing led to the identification of the variant of uncertain significance, namely, c.589-9_589-6delGTTT in the MLH1 gene. Further investigation revealed that this variant was likely pathogenetic. Subsequent next-generation sequencing panel analysis revealed the presence of two variants of uncertain significance in the ATM gene. We conclude that the phenotype of our index case is likely the result of a synergistic effect of these identified variants. Future studies will allow us to understand how risk alleles in different colorectal-cancer-prone genes interact with each other to increase an individual’s risk of developing cancer.https://www.mdpi.com/1422-0067/24/6/5970ATM geneLynch syndromeMMR genesuncertain significance variantssynergist effect of risk alleles |
| spellingShingle | Antonio Nolano Giovanni Battista Rossi Valentina D’Angelo Raffaella Liccardo Marina De Rosa Paola Izzo Francesca Duraturo Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion International Journal of Molecular Sciences ATM gene Lynch syndrome MMR genes uncertain significance variants synergist effect of risk alleles |
| title | Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion |
| title_full | Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion |
| title_fullStr | Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion |
| title_full_unstemmed | Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion |
| title_short | Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion |
| title_sort | germline variants in mlh1 and atm genes in a young patient with msi h in a precancerous colonic lesion |
| topic | ATM gene Lynch syndrome MMR genes uncertain significance variants synergist effect of risk alleles |
| url | https://www.mdpi.com/1422-0067/24/6/5970 |
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