Table 1. List of three CMMR-D patients with agenesis of the corpus callosum and cerebral heterotopias.
| Patient | Gene | Mutations | Family history | Malignant tumors (age in years at diagnosis or at death of disease) | Signs of neurofibromatosis or other non-neoplastic features | Results of microsatellite instability (MSI) | Results of immunohistochemical analysis in tumor | Reference |
|---|---|---|---|---|---|---|---|---|
| 1 | PMS2 | c.(2397_2400del)+(2397_2400del) p.(Ser801GlufsX15)+(Ser801GlufsX15) | Consanguineous parents (paternal grandfather and maternal grandmother are sibs); no FH of cancer (one brother died at early age of unknown cause) | B-cell NHL (9 years), muco-epidermoïd carcinoma of the parotis (11 years), T-cell NHL (11.5 years) | >10 CALMs; MRI-brain: ACC, interhemisferic cyst, heterotopia; decreased IgA levels (total 0.18 g/l); IgG and IgM in normal range with 7.7 and 0.84 g/l, respectively | No MSI in parotis cancer and surrounding normal parotid tissue and in T-cell NHL | MLH1/MSH2/MSH6/PMS2: +/+/+/− (in parotis cancer and in T-cell NHL) | This report |
| 2 | MLH1 | c.(218T>G)+(218T>G) p.(Leu73Arg)+(Leu73Arg) | No known consanguinity (parents both from same Pacific Island population); maternal grandfather (50 years), great aunt (48 years) and great-great grandfather (79 years) CRC; paternal FH unknown | Glioblastoma multiforme (3 years) T-cell lymphoblastic lymphoma (5.5 years) | >15 CALMs, renal cysts; MRI-brain: near complete ACC, interhemispheric cyst, frontal heterotopia, intracerebral cysts (angiomas?) | NA | MLH1/MSH2/MSH6/PMS2: −/+/+/− (in glioblastoma and in T-cell lymphoblastic lymphoma) | This report |
| 3 | PMS2 | c.(538−?_803+?del)+(1121dupA) p.(Glu180HisfsX30)+(Gln375AlafsX7) | No consanguinity, no FH of CRC | Anaplastic astrocytoma of the cervicothoracic spinal cord (3 years), T-cell lymphoblastic lymphoma (5.5 years) | No CALMs, capillary haemangioma; MRI-brain: ACC | NA | MLH1/MSH2/MSH6/PMS2: −(a)/+/+/− (in anaplastic astrocytoma) | This report |
| 4 | PMS2 | c.(1840A>T)+(1840A>T) p.(Lys614X)+(Lys614X) | Consanguineous parents (paternal and maternal grandfather are sibs); identical twin anaplastic oligodendroglioma (no ACC!), mother endometrial cancer (56 years), maternal grandmother and maternal great-grandmother and uncle CRC (52, 80 and 60 years), paternal grandmother cancer of paranasal sinus (62 years) | Adenocarcinoma of sigmoid colon (14 years) astrocytoma grade III (19 years) | Multiple ‘congenital compound nevi' (CALMs); MRI-brain: ACC; hypogammaglobulinemia as infant (attributed to Transcobalamin II deficiency) | No MSI in glioma and CRC | MLH1/MSH2/MSH6/PMS2: +/+/+/− (in glioma, CRC and normal brain and colonic tissue) | Gururangan et al29 |
Abbreviations: ACC, agenesis of corpus callosum; CALMs, café-au lait macules; CMMR-D, constitutional mismatch repair deficiency; CRC, colorectal cancer; FH, family history; MSI, microsatellite instability; NA, not analyzed; NHL, non-hodgkin lymphoma; +, positive IHC staining; −, negative IHC staining.
GenBank reference sequences for PMS2 and MLH1 are NM_000535.5 and NM_000249.3, respectively.
a
MLH1 loss only in the tumor cells but not in the non-neoplastic cells.