A Family with Autosomal Dominant Distal Renal Tubular Acidosis Presents with Atypical Phenotype Caused by a Missence Mutation (R388C) of the Human Kidney Anion Exchanger

Nephron ◽  
2018 ◽  
Vol 141 (3) ◽  
pp. 207-212 ◽  
Author(s):  
Dongdong Wang ◽  
Yang Yu ◽  
Renee Wang ◽  
Yitong Cai ◽  
Yacai Li ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Autosomal Dominant ◽  
Human Kidney ◽  
Distal Renal Tubular Acidosis ◽  
Renal Tubular ◽  
Atypical Phenotype

Impaired trafficking of distal renal tubular acidosis mutants of the human kidney anion exchanger kAE1

2002 ◽  
Vol 282 (5) ◽  
pp. F810-F820 ◽  
Author(s):  
Janne A. Quilty ◽  
Jing Li ◽  
Reinhart A. Reithmeier
Keyword(s):  
Cell Surface ◽  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Human Kidney ◽  
Distal Renal Tubular Acidosis ◽  
Dominant Negative ◽  
Cell Surface Expression ◽  
Dominant Negative Effect ◽  
Inherited Disease ◽  
Renal Tubular

Distal renal tubular acidosis (dRTA) is an inherited disease characterized by the failure of the kidneys to appropriately acidify urine and is associated with mutations in the anion exchanger (AE)1 gene. The effect of the R589H dRTA mutation on the expression of the human erythroid AE1 and the truncated kidney form (kAE1) was examined in transfected human embryonic kidney 293 cells. AE1, AE1 R589H, and kAE1 were present at the cell surface, whereas kAE1 R589H was located primarily intracellularly as shown by immunofluorescence, cell surface biotinylation, N-glycosylation, and anion transport assays. Coexpression of kAE1 R589H reduced the cell surface expression of kAE1 and AE1 by a dominant-negative effect, due to heterodimer formation. The mutant AE1 and kAE1 bound to an inhibitor affinity resin, suggesting that they were not grossly misfolded. Other mutations at R589 also prevented the formation of the cell surface form of kAE1, indicating that this conserved arginine residue is important for proper trafficking. The R589H dRTA mutation creates a severe trafficking defect in kAE1 but not in erythroid AE1.

scholarly journals Autosomal dominant distal renal tubular acidosis caused by a mutation in the anion exchanger 1 gene in a Japanese family

2015 ◽  
Vol 4 (2) ◽  
pp. 218-222 ◽  
Author(s):  
Naoko Ito ◽  
Kenji Ihara ◽  
Tomohiro Kamoda ◽  
Satoshi Akamine ◽  
Kentaro Kamezaki ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Autosomal Dominant ◽  
Distal Renal Tubular Acidosis ◽  
Japanese Family ◽  
Anion Exchanger 1 ◽  
Renal Tubular

scholarly journals Impaired trafficking of human kidney anion exchanger (kAE1) caused by hetero-oligomer formation with a truncated mutant associated with distal renal tubular acidosis

2002 ◽  
Vol 368 (3) ◽  
pp. 895-903 ◽  
Author(s):  
Janne A. QUILTY ◽  
Emmanuelle CORDAT ◽  
Reinhart A.F. REITHMEIER
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Human Kidney ◽  
Distal Renal Tubular Acidosis ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Wild Type ◽  
Hek 293 ◽  
Oligomer Formation ◽  
Renal Tubular

Autosomal dominant distal renal tubular acidosis (dRTA) has been associated with several mutations in the anion exchanger AE1 gene. The effect of an 11-amino-acid C-terminal dRTA truncation mutation (901 stop) on the expression of kidney AE1 (kAE1) and erythroid AE1 was examined in transiently transfected HEK-293 cells. Unlike the wild-type proteins, kAE1 901 stop and AE1 901 stop mutants exhibited impaired trafficking from the endoplasmic reticulum to the plasma membrane as determined by immunolocalization, cell-surface biotinylation, oligosaccharide processing and pulse—chase experiments. The 901 stop mutants were able to bind to an inhibitor affinity resin, suggesting that these mutant membrane proteins were not grossly misfolded. Co-expression of wild-type and mutant kAE1 or AE1 resulted in intracellular retention of the wild-type proteins in a pre-medial Golgi compartment. This dominant negative effect was due to hetero-oligomer formation of the mutant and wild-type proteins. Intracellular retention of kAE1 in the α-intercalated cells of the kidney would account for the impaired acid secretion into the urine characteristic of dRTA.

scholarly journals Trafficking Defects of a Novel Autosomal Recessive Distal Renal Tubular Acidosis Mutant (S773P) of the Human Kidney Anion Exchanger (kAE1)

2004 ◽  
Vol 279 (39) ◽  
pp. 40960-40971 ◽  
Author(s):  
Saranya Kittanakom ◽  
Emmanuelle Cordat ◽  
Varaporn Akkarapatumwong ◽  
Pa-thai Yenchitsomanus ◽  
Reinhart A. F. Reithmeier
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Autosomal Recessive ◽  
Human Kidney ◽  
Distal Renal Tubular Acidosis ◽  
Trafficking Defects ◽  
Renal Tubular

The association between familial distal renal tubular acidosis and mutations in the red cell anion exchanger (band 3, AE1) gene

1998 ◽  
Vol 76 (5) ◽  
pp. 723-728 ◽  
Author(s):  
Lesley J Bruce ◽  
Robert J Unwin ◽  
Oliver Wrong ◽  
Michael JA Tanner
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Autosomal Dominant ◽  
Collecting Duct ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Xenopus Laevis Oocytes ◽  
Red Cell ◽  
Transport Activity ◽  
Renal Tubular

In distal renal tubular acidosis (dRTA) the tubular secretion of hydrogen ion in the distal nephron is impaired, leading to the development of metabolic acidosis, frequently accompanied by hypokalemia, nephrocalcinosis, and metabolic bone disease. The condition can be familial, when it is usually inherited as an autosomal dominant, though there is a rarer autosomal recessive form associated with nerve deafness. It has been shown that the autosomal dominant form of dRTA is associated with a defect in the anion exchanger (AE1) of the renal collecting duct intercalated cell. This transporter is a product of the same gene (AE1) as the erythrocyte anion exchanger, band 3. In this review we will look at the evidence for this association. Studies of genomic DNA from families with this disorder have shown, both by genetic linkage studies and by DNA sequencing, that affected individuals are heterozygous for mutations in the AE1 gene whilst unaffected family members have a normal band 3 sequence. Mutations have been found in the region of proposed helices 6 and 7 of the membrane domain of band 3 and involve amino acids Arg-589 and Ser-613, and in the COOH-terminal domain of band 3. Studies of red cell band 3 from these families have provided information on the effect these mutations have on the structure and function of erythrocyte band 3. Expression studies of the erythroid and kidney isoforms of the mutant AE1 proteins, in Xenopus laevis oocytes, have shown that they retained chloride transport activity, suggesting that the disease in the dRTA families is not related simply to the anion transport activity of the mutated proteins. A possible explanation for the dominant effect of these mutant AE1 proteins in the kidney cell is that these mutations affect the targeting of AE1 from the basolateral to the apical membrane of the alpha-intercalated cell.Key words: erythrocyte, kidney, acidosis.

A Novel Mutation in the Anion Exchanger 1 Gene Is Associated With Familial Distal Renal Tubular Acidosis and Nephrocalcinosis

PEDIATRICS ◽  
2003 ◽  
Vol 112 (6) ◽  
pp. 1361-1367 ◽  
Author(s):  
L. Cheidde ◽  
T. C. Vieira ◽  
P. R. M. Lima ◽  
S. T. O. Saad ◽  
I. P. Heilberg
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Novel Mutation ◽  
Distal Renal Tubular Acidosis ◽  
Anion Exchanger 1 ◽  
Renal Tubular

Dominant and Recessive Distal Renal Tubular Acidosis Mutations of Kidney Anion Exchanger 1 Induce Distinct Trafficking Defects in MDCK Cells

Traffic ◽  
2005 ◽  
Vol 7 (2) ◽  
pp. 117-128 ◽  
Author(s):  
Emmanuelle Cordat ◽  
Saranya Kittanakom ◽  
Pa-thai Yenchitsomanus ◽  
Jing Li ◽  
Kai Du ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Mdck Cells ◽  
Distal Renal Tubular Acidosis ◽  
Anion Exchanger 1 ◽  
Trafficking Defects ◽  
Renal Tubular

Trafficking defect of mutant kidney anion exchanger 1 (kAE1) proteins associated with distal renal tubular acidosis and Southeast Asian ovalocytosis

2006 ◽  
Vol 350 (3) ◽  
pp. 723-730 ◽  
Author(s):  
Nunghathai Sawasdee ◽  
Wandee Udomchaiprasertkul ◽  
Sansanee Noisakran ◽  
Nanyawan Rungroj ◽  
Varaporn Akkarapatumwong ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Southeast Asian ◽  
Distal Renal Tubular Acidosis ◽  
Anion Exchanger 1 ◽  
Renal Tubular

scholarly journals Anion exchanger 1 mutations associated with distal renal tubular acidosis in the Thai population

2003 ◽  
Vol 48 (9) ◽  
pp. 451-456 ◽  
Author(s):  
Pa-thai Yenchitsomanus ◽  
Nunghathai Sawasdee ◽  
Atchara Paemanee ◽  
Thitima Keskanokwong ◽  
Somkiat Vasuvattakul ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Distal Renal Tubular Acidosis ◽  
Thai Population ◽  
Anion Exchanger 1 ◽  
Renal Tubular

Distal Renal Tubular Acidosis Associated With Anion Exchanger 1 Mutations in Children in Thailand

2007 ◽  
Vol 49 (6) ◽  
pp. 841-850.e1 ◽  
Author(s):  
Sookkasem Khositseth ◽  
Apiwan Sirikanerat ◽  
Kulruedee Wongbenjarat ◽  
Sauwalak Opastirakul ◽  
Siri Khoprasert ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Distal Renal Tubular Acidosis ◽  
Anion Exchanger 1 ◽  
Renal Tubular
Sign in / Sign up

Export Citation Format

Share Document