Diagnostic challenges in a child with early onset desmoplastic medulloblastoma and homozygous variants in MSH2 and MSH6
| العنوان: | Diagnostic challenges in a child with early onset desmoplastic medulloblastoma and homozygous variants in MSH2 and MSH6 |
|---|---|
| المؤلفون: | Triantafyllia Brozou, Olivier Lascols, Michaela Kuhlen, Chrystelle Colas, Julia Taeubner, Christine Fauth, Jessica I. Hoell, Katharina Wimmer, Joerg Felsberg, Jasmin C. Riemer, Sebastian Ginzel, Arndt Borkhardt, Martine Muleris, Michael Gombert |
| المساهمون: | Department of Medical Genetics, Medical University of Vienna, Vienna, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Division of Clinical Genetics, Department of Medical Genetics, Molecular and and Clinical Pharmacology, Innsbruck Medical University [Austria] (IMU), Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University |
| المصدر: | European Journal of Human Genetics European Journal of Human Genetics, Nature Publishing Group, 2018, 26 (3), pp.440-444. ⟨10.1038/s41431-017-0071-5⟩ |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], education, Brief Communication, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Cell Line, Tumor, Genetics, Humans, Medicine, Genetic Testing, Cerebellar Neoplasms, Cells, Cultured, Genetics (clinical), business.industry, Desmoplastic medulloblastoma, Homozygote, Infant, Microsatellite instability, medicine.disease, Phenotype, 3. Good health, DNA-Binding Proteins, MSH6, MutS Homolog 2 Protein, 030104 developmental biology, MSH2, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, DNA mismatch repair, business, Medulloblastoma |
| الوصف: | Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer susceptibility syndrome caused by biallelic germline mutations in one of the mismatch repair (MMR) genes. The spectrum of CMMRD-associated tumours is very broad and many CMMRD patients additionally display signposting non-neoplastic features, most frequently café-au-lait macules and other pigmentation alterations. We report on a 13-month-old girl suspected of having CMMRD due to a desmoplastic medulloblastoma and a striking skin pigmentation that included multiple café-au-lait macules, hypopigmented areas and Mongolian spots. Whole-exome sequencing revealed homozygosity for MSH2 variant p.(Leu92Val) and MSH6 variant p.(Val809del), both variants of uncertain significance (VUS). Immunohistochemical analysis of the tumour tissue showed expression of all four MMR proteins and gMSI testing was negative. However, functional assays demonstrated that the cells of the patient displayed methylation tolerance and ex vivo microsatellite instability, which unequivocally confirmed the diagnosis of CMMRD. Taken together, the results render the MSH2 variant unlikely to be responsible for the phenotype, while they are compatible with MSH6-associated CMMRD. This case illustrates the diagnostic strategy of confirming CMMRD syndrome in patients with VUS. |
| تدمد: | 1476-5438 1018-4813 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9608fd9bf63c1ef0c72227b6627a182 https://doi.org/10.1038/s41431-017-0071-5 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d9608fd9bf63c1ef0c72227b6627a182 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765438 10184813 |
|---|