GI tract tumours
Gene: MBD4- Palles et al. 2022 (PMID: 35460607) reported on 5 individuals from 4 families with biallelic MBD4 variants who had a personal and/or family history of adenomatous colorectal polyposis (5/5), AML (1/5 personal), and uveal melanoma (2/5 personal). Consistent with previous studies, MBD4-deficient colorectal adenomas showed a significantly increased mutational burden compared to sporadic colorectal tumours, which were mostly attributable to an excess of CpG>TpG transitions.
- Sanders et al. 2018 (PMID: 30049810) demonstrated in 3 individuals with AML (including 2 sibs) and LoF variants in MBD4, that MBD4-deficient cancers exhibit a unique mutational signature with high burden of CpG>TpG transitions. Note that PMID: 32239153 refer to the same individuals.
The MBD4-related hypermutator phenotype has also been detected in Mbd4 mutant mice (PMID:12417741) and other human cancers such as uveal melanoma and colorectal tumours (PMID: 29760383; 32239153; 31322271).Created: 5 Jul 2022, 3:13 p.m. | Last Modified: 5 Jul 2022, 3:13 p.m.
Panel Version: 1.19
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Multi-organ tumour predisposition syndrome; Adenomatous colorectal polyposis; Colorectal cancer; Acute myeloid leukemia; Uveal melanoma
Publications
Bi-allelic loss of function mutation carriers at high risk of early onset AML, colorectal polyposis an uveal melanoma. Heterozygous monoallelic carriers at no significantly increased risk in data so far.
Sources: LiteratureCreated: 30 Jun 2022, 10:47 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
polyposis; CRC; AML; MDS; UVM
Publications
Gene: mbd4 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MBD4 were changed from polyposis; CRC; AML; MDS; UVM to Multi-organ tumour predisposition syndrome; Adenomatous colorectal polyposis; Colorectal cancer; Acute myeloid leukemia; Uveal melanoma
Publications for gene: MBD4 were set to 35460607
gene: MBD4 was added gene: MBD4 was added to GI tract tumours. Sources: Literature Mode of inheritance for gene: MBD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBD4 were set to 35460607 Phenotypes for gene: MBD4 were set to polyposis; CRC; AML; MDS; UVM Penetrance for gene: MBD4 were set to Complete Review for gene: MBD4 was set to GREEN