0000000000356919
AUTHOR
Nine V A M Knoers
Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.
Peters, T.A./0000-0001-8443-5500; van Beersum, Sylvia E.C./0000-0002-4552-2908; Cremers, Frans/0000-0002-4954-5592; Roepman, Ronald/0000-0002-5178-8163 WOS: 000247619800019 PubMed: 17558407 Protein- protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis ( NPHP), Leber congenital amaurosis, Senior- Loken syndrome ( SLSN) or Joubert syndrome ( JBTS)(1-6). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1- like protein ( RPGRIP1L) is a homolog of RPGRIP1 ( RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis(7,8). We show t…
Misfolded vasopressin V2 receptors caused by extracellular point mutations entail congenital nephrogenic diabetes insipidus.
Vasopressin V2 receptor mutants from three different patients with congenital nephrogenic diabetes insipidus phenotypes were investigated after expression in COS cells. The amino acid exchanges within the human V2 receptor are located in the second extracellular loop (T204N, Y205C and V206D). Confocal microscopy showed that all receptor mutants were strongly expressed but mainly located within the cell. Residual binding capacity for the antidiuretic hormone arginine vasopressin (AVP) could only be detected for the T204N mutant and was 10-fold lower than for the wild-type receptor. Stimulation of transfected cells with 1 microM AVP showed that the T204N mutant was able to activate the adenyl…
Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA
Contains fulltext : 248375.pdf (Publisher’s version ) (Closed access) BACKGROUND: Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. Gitelman syndrome is caused by biallelic pathogenic variants in SLC12A3, encoding the Na(+)-Cl(-) cotransporter (NCC) expressed in the distal convoluted tubule. Pathogenic variants of CLCNKB, HNF1B, FXYD2, or KCNJ10 may result in the same renal phenotype of Gitelman syndrome, as they can lead to reduced NCC activity. For approximately 10 percent of patients with a Gitelman syndrome phenotype, the genotype is unknown. METHODS: We identified mitochondrial DNA (mtDNA) variants in th…