As recent publication in the Journal of the American Society of Nephrology from research carried out by the Exeter genetics group and an international group of collaboratorshas identified variants in the PMM2 gene as a cause of hyperinsulinism and polycystic kidney disease.
All of the patients in the study were affected with hyperinsulinism, which can cause dangerously low blood sugar, and fluid filled sacks on their kidneys, called cysts, which can affect how well the kidneys function. The PMM2 gene encodes the instructions for making a protein called phosphomannomutase 2, and this new finding implicates the gene in both hyperinsulinism and polycystic kidney disease. All the affected individuals carried a heterozygous variant just outside the PMM2 gene that is essential for regulating it, and either had two copies of this variant or also had a variant within the gene that affected the protein sequence. The specific phenotype of the patients differs from individuals with two variants in PMM2 affecting the protein, and this study has increased the number of genetic causes of both hyperinsulinism and polycystic kidney disease, as well as providing new information on the regulation of PMM2.
