A de novo pathogenic variant in the MSH6 gene in a 52 years-old woman

Springer Science and Business Media LLC - 2021
Elise Pierre-Noël1, Fabrice Airaud1, Estelle Cauchin2,3, Céline Garrec1, Ingrid Ricordeau1, Clémence Michon4, Olivier Kerdraon5, Stéphane Bezieau1, Caroline Abadie2
1Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, Nantes, France
2Institut de Cancérologie de l'Ouest, Saint-Herblain, France
3Centre Hospitalier Universitaire de Nantes, Institut des maladies de l’appareil digestif, Nantes, France
4Institut de Cancérologie de l’Ouest, laboratoire d’Oncopharmacologie et pharmacogénétique, Angers, France
5Département de pathologie tissulaire et moléculaire, Institut de Cancérologie de l’Ouest, Saint-Herblain, France

Tóm tắt

Lynch syndrome (LS) is a condition which predisposes individuals primarily to early-onset colorectal and endometrial cancer. LS is characterized by a germline pathogenic variant in one of the MMR (MisMatch Repair) gene, inducing a phenotype of microsatellite instability in the tumor, which may be associated with a loss of expression of MMR proteins detected by standard immunohistochemistry on tumor tissue. Most of the time, LS is inherited from a parent in whom the condition may not be known due to incomplete penetrance, but de novo pathogenic variant is a rare occurrence. Here, we describe the case of a 52-year-old woman with no family history of LS, referred to the genetics department for colorectal cancer at the age of 50. Genetic analysis revealed a de novo germline pathogenic variant in the MSH6 gene. To date, this case is only the second report of a de novo pathogenic variant in the MSH6 gene in Lynch syndrome. De novo mutations have been extensively studied over the past years, but little is known about their origin and mechanism of occurrence in MMR genes. However, knowledge of mutation status allows better cancer risk management for the patient and an appropriate genetic testing and counseling for her family.

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