Blood Journal
Leading the way in experimental and clinical research in hematology

CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune mediated polyneuropathy

  1. Yoram Nevo1,
  2. Bruria Ben-Zeev2,
  3. Adi Tabib3,
  4. Rachel Straussberg4,
  5. Yair Anikster5,
  6. Zamir Shorer6,
  7. Aviva Fattal-Valevski7,
  8. Asaf Ta-Shma8,
  9. Sharon Aharoni4,
  10. Malcolm Rabie1,
  11. Shamir Zenvirt8,
  12. Hanoch Goldshmidt9,
  13. Yakov Fellig9,
  14. Avraham Shaag8,
  15. Dror Mevorach3,*, and
  16. Orly Elpeleg8
  1. 1 Neuropediatric Unit, Hadassah, Hebrew University Medical Center., Jerusalem, Israel;
  2. 2 Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel;
  3. 3 Rheumatology Research Center and Department of Medicine, Hadassah, Hebrew University Medical Center, Jerusalem, Israel;
  4. 4 Neurogenetic Clinic, Department of Child Neurology, Schneider's Children Medical Center, Petah-Tikva, Israel;
  5. 5 Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel;
  6. 6 Neuropediatric Unit, Soroka Medical Center, Ben Gurion University, Beer-Sheva, Israel;
  7. 7 Pediatric Neurology Unit, Dana Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel;
  8. 8 Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel;
  9. 9 Department of Pathology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
  1. * Corresponding author; email: mevorachd{at}


CD59 deficiency is a common finding in red and white blood cells in patients with chronic hemolysis suffering from paroxysmal nocturnal hemoglobinuria (PNH) where acquired mutation in the PIGA gene leads to membrane loss of GPI-anchored membrane proteins, including CD59. The current study objective was the elucidation of the molecular basis of childhood familial chronic Coombs' negative hemolysis and relapsing polyneuropathy, presenting as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in infants of North-African Jewish origin from four unrelated families. A founder mutation was searched using homozygosity mapping followed by exome sequencing. The expression of CD59, CD55 and CD14 was examined in blood cells by flow cytometry followed by western blot of the CD59 protein. A homozygous missense mutation, p.Cys89Tyr in CD59, was identified in all the patients. The mutation segregated with the disease in the families and had a carrier rate of 1:66 among Jews of North-African origin. The mutated protein was present in the patients' cells in reduced amount and was undetectable on the membrane surface. The Cys89Tyr mutation in CD59 is associated with a failure of proper localization of CD59 protein in the cell surface. This is clinically manifested in infancy by chronic hemolysis and relapsing peripheral demyelinating disease.

  • Submitted July 16, 2012.
  • Accepted October 4, 2012.