Abstract |
Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion ( chloride-bicarbonate) exchanger 1 may result in familial distal renal tubular acidosis ( dRTA) in association with membrane defect hemolytic anemia. Seven children presenting with hyperchloremic normal anion gap metabolic acidosis, failure to thrive, and compensated hemolytic anemia were studied. Analysis of red cell AE1/Band 3 surface expression by Eosin 5'-maleimide (E5M) was performed in patients and their family members using flow cytometry. Genetic studies showed that all patients carried a common SLC4A1 mutation, c.2573C>A; p.Ala858Asp in exon 19, found as homozygous (A858D/A858D) mutation in the patients and heterozygous (A858D/N) in the parents. Analysis by flowcytometry revealed a single uniform fluorescence peak, with the mean channel fluorescence (MCF) markedly reduced in cases with homozygous mutation, along with a left shift of fluorescence signal but was only mildly reduced in the heterozygous state. Red cell morphology showed striking acanthocytosis in the homozygous state [patients] and only a mild acanthocytosis in heterozygous state [parents]. In conclusion, this is the first description of a series of homozygous cases with the A858D mutation. The E5M flowcytometry test is specific for reduction in the Band 3 membrane protein and was useful in conjunction with a careful morphological examination of peripheral blood smears in our patient cohort.
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Authors | Naglaa A Fawaz, Ismail O Beshlawi, Shoaib Al Zadjali, Hamed K Al Ghaithi, Mohamed A Elnaggari, Ibtisam Elnour, Yasser A Wali, Bushra B Al-Said, Jalil U Rehman, Anil V Pathare, Huxley Knox-Macaulay, Salam S Alkindi |
Journal | European journal of haematology
(Eur J Haematol)
Vol. 88
Issue 4
Pg. 350-5
(Apr 2012)
ISSN: 1600-0609 [Electronic] England |
PMID | 22126643
(Publication Type: Journal Article)
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Copyright | © 2012 John Wiley & Sons A/S. |
Chemical References |
- Anion Exchange Protein 1, Erythrocyte
- Protein Isoforms
- SLC4A1 protein, human
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Topics |
- Acidosis, Renal Tubular
(genetics)
- Anemia, Hemolytic
(genetics)
- Anion Exchange Protein 1, Erythrocyte
(genetics)
- Child, Preschool
- Cytoskeleton
(metabolism)
- DNA Mutational Analysis
- Female
- Homozygote
- Humans
- Infant
- Male
- Mutation
- Neuroacanthocytosis
(genetics)
- Oman
- Protein Isoforms
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