Genetic Epilepsy

Gene: PMM2

Green List (high evidence)

Association with HIPKD:
Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.

Created: 26 Jul 2022, 1:24 a.m. | Last Modified: 26 Jul 2022, 1:24 a.m.

Panel Version: 1.173

CDG: Well established gene-disease association.

Created: 19 Jul 2021, 2:20 a.m. | Last Modified: 26 Jul 2022, 1:24 a.m.

Panel Version: 1.173

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Ia (MIM#212065); Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related

Publications

• 28108845
• 28373276
• 32595772

I don't know

Encodes for phosphomannomutase 2 required for glycosylation. Not a ciliopathy gene however CDG has many overlapping features with ciliopathy. Left as Amber.

PMID: 28108845: Review article. Well reported gene causing CDG. >700 patients reported

PMID: 25497157; Many patients reported. Similar features as ciliopathies
Sources: Expert Review

Created: 6 May 2020, 1:19 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Ia (MIM#212065)

Publications

• 28108845