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- Title
Cystic kidney diseases associated with mutations in phosphomannomutase 2 promotor: a large spectrum of phenotypes.
- Authors
Dorval, Guillaume; Jeanpierre, Cécile; Morinière, Vincent; Tournant, Carole; Bessières, Bettina; Attié-Bittach, Tania; Amiel, Jeanne; Spaggari, Emmanuel; Ville, Yves; Merieau, Elodie; Gubler, Marie-Claire; Saunier, Sophie; Heidet, Laurence
- Abstract
Background: Co-occurrence of polycystic kidney disease and hyperinsulinemic hypoglycemia has been reported in children in a few families associated with a variant in the promotor of the PMM2 gene, at position -167 upstream of the coding sequence. PMM2 encodes phosphomannomutase 2, a key enzyme in N-glycosylation. While biallelic coding PMM2 mutations are involved in congenital disorder of glycosylation CDG1A, that particular variant in the promoter of the gene, either in the homozygous state or associated with a mutation in the coding exons of the gene, is thought to restrict the N-glycosylation defect to the kidney and the pancreas. Methods: Targeted exome sequencing of a panel of genes involved in monogenic kidney diseases. Results: We identified a PMM2 variant at position -167 associated with a pathogenic PMM2 variant in the coding exons in 3 families, comprising 6 cases affected with a cystic kidney disease. The spectrum of phenotypes was very broad, from extremely enlarged fetal cystic kidneys in the context of a COACH-like syndrome, to isolated cystic kidney disease with small kidneys, slowly progressing toward kidney failure in adulthood. Hypoglycemia was reported only in one case. Conclusion: These data show that the PMM2 promotor variation, in trans of a PMM2 coding mutation, is associated with a wide spectrum of kidney phenotypes, and is not always associated with extra-renal symptoms. When present, extra-renal defects may include COACH-like syndrome. These data prompt screening of PMM2 in unresolved cases of fetal hyperechogenic/cystic kidneys as well as in cystic kidney disease in children and adults.
- Subjects
GENETIC mutation; SEQUENCE analysis; GLYCOSYLATION; KIDNEY failure; GENETIC variation; INBORN errors of carbohydrate metabolism; TRANSFERASES; HYPOGLYCEMIA; CYSTIC kidney disease; PHENOTYPES; DISEASE risk factors; DISEASE complications
- Publication
Pediatric Nephrology, 2021, Vol 36, Issue 8, p2361
- ISSN
0931-041X
- Publication type
Article
- DOI
10.1007/s00467-021-04953-9