SLC4A1 – Cryohydrocytosis

SLC4A1 encodes the erythrocyte band 3 anion exchanger (AE1) and heterozygous mutations cause dominantly inherited cryohydrocytosis, a temperature-dependent form of hereditary stomatocytosis. Two unrelated British families were reported with a c.2191T>C (p.Ser731Pro) variant segregating with red cell lysis at low temperatures, a 5–6-fold increase in passive Na⁺/K⁺ permeability at 37 °C, shifted permeability minimum to 23 °C and pseudohyperkalaemia on cold storage (PMID:10554820). The phenotype is consistent with impaired AE1-mediated anion exchange and membrane stability under physiologic conditions. No targeted molecular assays of p.Ser731Pro have been published, and there are no conflicting reports. Further studies are needed to expand the genotype–phenotype correlations and inform clinical management.

Key Take-home: Dominant c.2191T>C (p.Ser731Pro) in SLC4A1 causes cryohydrocytosis, guiding molecular diagnosis in temperature-sensitive hemolytic anemia.

References

• British journal of haematology • 1999 • Two British families with variants of the 'cryohydrocytosis' form of hereditary stomatocytosis. PMID:10554820

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