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Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells

Bruce, L. J., Wrong, O., Toye, A. M., Young, Mark Thomas, Ogle, G., Ismail, Z., Sinha, A. K., McMaster, P., Hwaihwanje, I., Nash, G. B., Hart, S., Lavu, E., Palmer, R., Othman, A., Unwin, R. J. and Tanner, M. J. A. 2000. Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells. Biochemical Journal 350 (1) , pp. 41-51.

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Abstract

We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to be restricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH301 Biology
Uncontrolled Keywords: erythrocyte, membrane, anion exchanger
Additional Information: Correction printed in vol 351, p. 839 at http://www.biochemj.org/bj/351/bj3510839w.htm: "On p. 50, left-hand column, line 18, the sentence ''No band 3 mutation, causally related to dRTA, has yet been reported in either occidental or oriental subjects'' should be replaced by: ''Indeed no band 3 mutation, causally related to dRTA, has yet been reported both in occidental and oriental subjects''."
Publisher: Biochemical Society
ISSN: 0264-6021
Last Modified: 02 May 2019 12:13
URI: http://orca.cf.ac.uk/id/eprint/57849

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