title: MSI detection and its pitfalls in CMMRD syndrome in a family with a bi-allelic MLH1 mutation.
abstract: The constitutional MisMatch Repair deficiency (CMMRD) syndrome is one of the inherited cancer predisposition syndromes. More than two-third patients belonging to a CMMRD family are diagnosed mainly in the first decade with brain cancers and/or hematological malignancies. This syndrome is due to bi-allelic germline mutations in genes of the MMR pathway (MLH1, MSH2, MSH6 or PMS2). Our family report begins with the index case presenting initially with a medulloblastoma, which was even the two relapses in complete remission, when she was diagnosed for an AML. She died after bone marrow transplantation from toxicity. The family history was progressively established when her uncle was diagnosed for a colonic cancer and a cousin for a brain tumor. Surprisingly, her father had an atypical sarcoma but her brother also presented a lymphoma followed by a gliomatosis cerebri. A new MLH1 bi-allelic mutation was identified in this family. More than the diagnostic difficulties, this family report illustrates the complexity of the microsatellite instability detection in CMMRD patients, which has to be discussed further to a more accurate diagnosis in the pediatric setting, and address the question of the proper diagnostic tool to use in such genetic background with hypermutated tumors.
authors.affiliation: Laboratoire de Biochimie et de Biologie Moléculaire, CHRU Hautepierre Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France.|EA 3430, Université de Strasbourg, "Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie", 3, Avenue Molière, 67000, Strasbourg, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Inserm U614, Faculté de Médecine, Institut de Recherche Biomédicale, Université de Rouen, 22, Boulevard Gambetta, 76183, Rouen, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Bougeard
authors.affiliation: Département de Radiologie II, CHRU Hautepierre Strasbourg, 1, Avenue Molière, 67098, Strasbourg Cedex, France.
authors.forename: Meriam
authors.initials: M
authors.lastname: Koob
authors.affiliation: Laboratoire d'Anatomie Pathologique, CHRU Hautepierre Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France.
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Chenard
authors.affiliation: Laboratoire de Biochimie et de Biologie Moléculaire, CHRU Hautepierre Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Oncogénétique Moléculaire, Laboratoire de diagnostic génétique, Nouvel Hôpital Civil, 1, place de l'Hôpital, 67091, Strasbourg Cedex, France.|Oncogénétique: évaluation et suivi familial, Service d'hémato-Oncologie, Hôpital Civil, 1 place de l'hôpital, 67091, Strasbourg Cedex, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Maugard
authors.affiliation: EA 3430, Université de Strasbourg, "Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie", 3, Avenue Molière, 67000, Strasbourg, France. Natacha.entz-werle@chru-strasbourg.fr.|Service de Pédiatrie Onco-Hématologie, CHRU Hautepierre Strasbourg, 1 Avenue Molière, 67098, Strasbourg, France. Natacha.entz-werle@chru-strasbourg.fr.
authors.forename: Natacha
authors.initials: N
authors.lastname: Entz-Werle
mesh_terms: D001932:Brain Neoplasms / Q000209:etiology / Q000235:genetics*; D002648:Child; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1 / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000209:etiology / Q000235:genetics*; D010375:Pedigree
chemical_list: C501486:MLH1 protein, human; D000070957:MutL Protein Homolog 1
keywords: Childhood brain cancers; MLH1; MMR deficiency; MSI