ArticleEuropean journal of human genetics : EJHG2018
Diagnostic challenges in a child with early onset desmoplastic medulloblastoma and homozygous variants in MSH2 and MSH6.
Article in European journal of human genetics : EJHG, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Constitutional Mismatch Repair Deficiency, the Most Aggressive Cancer Predisposition Syndrome : Clinical Presentation, Surveillance, and Management.Journal of Korean Neurosurgical Society · 2025Article
- Rare single-nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome.Cancer reports (Hoboken, N.J.) · 2024Article
- Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors.International journal of molecular sciences · 2023Article
- Risk prediction in early childhood sonic hedgehog medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than 2 subgroups.Neuro-oncology · 2023Article
- Using comprehensive genomic and functional analyses for resolving genotype-phenotype mismatches in children with suspected CMMRD in Lebanon: an IRRDC study.Human genetics · 2023Article
- C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation.The Journal of clinical investigation · 2021Article
- The Challenge of Diagnosing Constitutional Mismatch Repair Deficiency Syndrome in Brain Malignancies from Young Individuals.International journal of molecular sciences · 2021Review
- Medulloblastoma genomics in the modern molecular era.Brain pathology (Zurich, Switzerland) · 2020Review
- Diagnosis of a case of homozygous constitutional MMR-deficiency by the use of a gene-panel in a non-consanguineous family: A case report.Biomedical reports · 2020Article
- Genetic Predisposition to Solid Pediatric Cancers.Frontiers in oncology · 2020Review
- Trio sequencing in pediatric cancer and clinical implications.EMBO molecular medicine · 2018Article
- Constitutional mismatch repair deficiency-associated brain tumors: report from the European C4CMMRD consortium.Neuro-oncology advancesArticle
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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