Cystic kidney diseases associated with mutations in phosphomannomutase 2 promotor: a large spectrum of phenotypes.
Pediatr Nephrol
; 36(8): 2361-2369, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33580824
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. Graphical Abstract.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Renais Policísticas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article