Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis.
Inatomi J
,
Horita S
,
Braverman N
,
Sekine T
,
Yamada H
,
Suzuki Y
,
Kawahara K
,
Moriyama N
,
Kudo A
,
Kawakami H
,
Shimadzu M
,
Endou H
,
Fujita T
,
Seki G
,
Igarashi T
.
???displayArticle.abstract???
Permanent isolated proximal renal tubular acidosis (pRTA) with ocular abnormalities is a systemic disease with isolated pRTA, short stature and ocular abnormalities. We identified a novel homozygous deletion of nucleotide 2,311 adenine in the kidney type Na+/HCO3- cotransporter (kNBC1) cDNA in a patient with permanent isolated pRTA. This mutation is predicted to result in a frame shift at codon 721 forming a stop codon after 29 amino acids anomalously transcribed from the SLC4A4 gene. Cosegregation of this mutation with the disease was supported by heterozygosity in the parents of the affected patient. The absence of this mutation in 156 alleles of 78 normal individuals indicates that this mutation is related to the disease and is not a common DNA sequence polymorphism. When injected into Xenopus oocytes, the mutant cRNA failed to induce electrogenic transport activity. In addition, immunofluorescence and Western blot analysis failed to detect the expression of the full-length protein in mutant-injected oocytes. Our results expand the spectrum of kNBC1 mutations in permanent isolated pRTA with ocular abnormalities and increase our understanding of the renal tubular mechanism that is essential for acid-base homeostasis.
Abuladze,
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
2000, Pubmed
Abuladze,
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
2000,
Pubmed
Abuladze,
Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.
1998,
Pubmed
,
Xenbase
Bevensee,
An electrogenic Na(+)-HCO(-)(3) cotransporter (NBC) with a novel COOH-terminus, cloned from rat brain.
2000,
Pubmed
,
Xenbase
Braverman,
A case report and review of band keratopathy.
1987,
Pubmed
Brenes,
Familial proximal renal tubular acidosis. A distinct clinical entity.
1977,
Pubmed
Burnham,
Cloning and functional expression of a human kidney Na+:HCO3- cotransporter.
1997,
Pubmed
Choi,
Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).
1999,
Pubmed
,
Xenbase
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
Donckerwolcke,
A case of bicarbonate-losing renal tubular acidosis with defective carboanhydrase activity.
1970,
Pubmed
Ducoudret,
The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: inhibition by tenidap and benzamil and effect of temperature on transport rate and stoichiometry.
2001,
Pubmed
,
Xenbase
Freedman,
Pancreatic acinar cell dysfunction in CFTR(-/-) mice is associated with impairments in luminal pH and endocytosis.
2001,
Pubmed
Heyer,
Stoichiometry of the rat kidney Na+-HCO3- cotransporter expressed in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase
Igarashi,
Persistent isolated proximal renal tubular acidosis--a systemic disease with a distinct clinical entity.
1994,
Pubmed
Igarashi,
Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.
1999,
Pubmed
Igarashi,
Unraveling the molecular pathogenesis of isolated proximal renal tubular acidosis.
2002,
Pubmed
Igarashi,
Novel nonsense mutation in the Na+/HCO3- cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma.
2001,
Pubmed
Kopelman,
Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas.
1988,
Pubmed
Krapf,
Cell pH and transepithelial H/HCO3 transport in the renal proximal tubule.
1993,
Pubmed
Lemann,
Acid and mineral balances and bone in familial proximal renal tubular acidosis.
2000,
Pubmed
Nash,
Renal tubular acidosis in infants and children. Clinical course, response to treatment, and prognosis.
1972,
Pubmed
Rodriguez Soriano,
Proximal renal tubular acidosis. A defect in bicarbonate reabsorption with normal urinary acidification.
1967,
Pubmed
Romero,
Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter.
1997,
Pubmed
,
Xenbase
Romero,
Electrogenic Na+/HCO3- cotransporters: cloning and physiology.
1999,
Pubmed
Saiki,
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
1988,
Pubmed
Satoh,
Localization of Na+-HCO-3 cotransporter (NBC-1) variants in rat and human pancreas.
2003,
Pubmed
Schmitt,
Immunolocalization of the electrogenic Na+-HCO-3 cotransporter in mammalian and amphibian kidney.
1999,
Pubmed
,
Xenbase
Soleimani,
Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes.
2000,
Pubmed
Soleimani,
Physiologic and molecular aspects of the Na+/H+ exchangers in health and disease processes.
1995,
Pubmed
Soriano,
Bicarbonate reabsorption and hydrogen ion excretion in children with renal tubular acidosis.
1967,
Pubmed
Usui,
Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis.
2001,
Pubmed
Usui,
Functional and molecular evidence for Na(+)-HCO3- cotransporter in human corneal endothelial cells.
1999,
Pubmed
Yamada,
Localization of NBC-1 variants in human kidney and renal cell carcinoma.
2003,
Pubmed
