Hereditary brain tumor with a homozygous germline mutation in PMS2: pedigree analysis and prenatal screening in a family with constitutional mismatch repair deficiency (CMMRD) syndrome

Baig, Shahid Mahmood; Fatima, Ambrin; Tariq, Muhammad; Khan, Tahir Naeem; Ali, Zafar; Faheem, Mohammad; Mahmood, Humera; Killela, Patrick; Waitkus, Matthew S.; He, Yiping; Zhao, Fangping; Wang, Sizhen; Jiao, Yuchen; Yan, Hai

doi:10.1007/s10689-018-0112-4

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…The proband was compound heterozygous for PMS2 ( 19 ). Another study in a five-generation Pakistani family revealed six affected individuals who died of brain tumors at very young ages, of which three had biallelic PMS2 mutations ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, associated with a germline mutation in PMS2

Merchant

Raygada²,

Pang³

et al. 2022

Front. Oncol.

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Most tumors, including brain tumors, are sporadic. However, a small subset of CNS tumors are associated with hereditary cancer conditions like Lynch Syndrome (LS). Here, we present a case of an oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and LS with a germline pathogenic PMS2 mutation. To our knowledge, this has only been reported in a few cases in the literature. While the family history is less typical of LS, previous studies have indicated the absence of a significant family history in patient cohorts with PMS2 mutations due to its low penetrance. Notably, only a handful of studies have worked on characterizing PMS2 mutations in LS, and even fewer have looked at these mutations in the context of brain tumor development. This report aims to add to the limited literature on germline PMS2 mutations and oligodendrogliomas. It highlights the importance of genetic testing in neuro-oncology.

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Section: Discussionmentioning

confidence: 99%

Case report: Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, associated with a germline mutation in PMS2

Merchant

Raygada²,

Pang³

et al. 2022

Front. Oncol.

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“…Specifically, loss of MMR protein immunoreaction is not only seen in tumor cells but also in normal cells. Moreover, in CMMRD brain malignancies the standard MSI analysis fails to show instability [ 2 , 7 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ] although the use of an extended Bethesda panel with 10 additional mononucleotide repeat markers has detected subtle frameshifts [ 61 ]. Nowadays, the use of MMR IHC is becoming increasingly widespread mainly due to universal LS screening of colorectal and endometrial tumors [ 67 , 68 ].…”

Section: Introductionmentioning

confidence: 99%

The Challenge of Diagnosing Constitutional Mismatch Repair Deficiency Syndrome in Brain Malignancies from Young Individuals

Carrato

Sanz

Muñoz-Mármol

et al. 2021

IJMS

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Biallelic germline mismatch repair (MMR) gene (MLH1, MSH2, MSH6, and PMS2) mutations are an extremely rare event that causes constitutional mismatch repair deficiency (CMMRD) syndrome. CMMRD is underdiagnosed and often debuts with pediatric malignant brain tumors. A high degree of clinical awareness of the CMMRD phenotype is needed to identify new cases. Immunohistochemical (IHC) assessment of MMR protein expression and analysis of microsatellite instability (MSI) are the first tools with which to initiate the study of this syndrome in solid malignancies. MMR IHC shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. However, MSI often fails in brain malignancies. The aim of this report is to draw attention to the peculiar IHC profile that characterizes CMMRD syndrome and to review the difficulties in reaching an accurate diagnosis by describing the case of two siblings with biallelic MSH6 germline mutations and brain tumors. Given the difficulties involved in early diagnosis of CMMRD we propose the use of the IHC of MMR proteins in all malignant brain tumors diagnosed in individuals younger than 25 years-old to facilitate the diagnosis of CMMRD and to select those neoplasms that will benefit from immunotherapy treatment.

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NGS-driven molecular diagnosis of heterogeneous hereditary neurological disorders reveals novel and known variants in disease-causing genes

et al. 2022

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Hereditary brain tumor with a homozygous germline mutation in PMS2: pedigree analysis and prenatal screening in a family with constitutional mismatch repair deficiency (CMMRD) syndrome

Cited by 3 publications

References 23 publications

Case report: Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, associated with a germline mutation in PMS2

Case report: Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, associated with a germline mutation in PMS2

The Challenge of Diagnosing Constitutional Mismatch Repair Deficiency Syndrome in Brain Malignancies from Young Individuals

NGS-driven molecular diagnosis of heterogeneous hereditary neurological disorders reveals novel and known variants in disease-causing genes

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