Inflammatory bowel disease

Gene: PMM2

Red List (low evidence)

PMM2 (phosphomannomutase 2)
EnsemblGeneIds (GRCh38): ENSG00000140650
EnsemblGeneIds (GRCh37): ENSG00000140650
OMIM: 601785, Gene2Phenotype
PMM2 is in 22 panels

1 review

Sarah Pantaleo (Victorian Clinical Genetics Services)

Red List (low evidence)

“A specific pattern of variation in PMM2 as a novel association of early-onset IBD with distinctive gastric pathology.”

Cohort of patients affected by hyperinsulinaemic hypoglycaemia and ARPKD with a specific underlying variant in the PMM2 promoter. Three of these patients additionally developed IBD in childhood and manifest a distinctive pattern of gastric antral disease involvement.

The authors describe the development of IBD in three patients with PMM2-HIPKD, with onset of IBD at 0, 6 and 10 years of age. IBD was of variable severity at onset. The organ level pattern of disease manifestations in PMM2-HIPKD-IBD may reflect a loss of cis-acting regulatory control by hepatocyte nuclear factor 4 alpha (HNF4A).

All three patients have the same genotype, two pathogenic variants (ClinVar): A promoter variant, c.-167G>T, in trans with c.422G>A; p.(Arg141His). The promoter region is not covered in gnomAD. c.422G>A is in gnomAD v2 891 hets, v3 557 hets.

Functional studies: Protein expression of PMM2 and HNF4A assessed by immunohistochemistry for two patients. Patient 1 there appeared to be reduced protein expression compared to the control, especially in the gastric antrum and colon, but for patient 2, the expression profile closely matched the control.

Observation of intestinal inflammation and gastric antral foveolar hyperplasia in three patients with identical pathogenic genetic variants in the PMM2 locus, from independent kindreds, extends the previously reported spectrum of PMM2-related HI/ARPKD disease. It identifies PMM2 as a potential novel Mendelian association of early-onset IBD. Estimate low penetrance of IBD of 10% based on 30 patients in the literature.
Sources: Literature
Created: 2 Mar 2023, 3:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Inflammatory bowel disease, hyperinsulinism, polycystic kidney disease

Publications

History Filter Activity

2 Mar 2023, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: pmm2 has been classified as Red List (Low Evidence).

2 Mar 2023, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PMM2 were changed from Inflammatory bowel disease, hyperinsulinism, polycystic kidney disease to Congenital disorder of glycosylation, type Ia, MIM# 212065; Inflammatory bowel disease, hyperinsulinism, polycystic kidney disease

2 Mar 2023, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: pmm2 has been classified as Red List (Low Evidence).

2 Mar 2023, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Sarah Pantaleo (Victorian Clinical Genetics Services)

gene: PMM2 was added gene: PMM2 was added to Inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PMM2 were set to 36773065 Phenotypes for gene: PMM2 were set to Inflammatory bowel disease, hyperinsulinism, polycystic kidney disease Penetrance for gene: PMM2 were set to Incomplete Review for gene: PMM2 was set to RED