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Published January 1, 2019 | Version v1
Journal article Open

Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry

Creators

  • 1. Ege Univ, Fac Med, Dept Pediat Hematol, Izmir, Turkey
  • 2. Erciyes Univ, Fac Med, Dept Pediat Immunol, Izmir, Turkey
  • 3. Ankara Childrens Hematol Oncol Training & Res Hos, Dept Pediat Immunol, Ankara, Turkey
  • 4. Necmettin Erbakan Univ, Meram Fac Med, Dept Pediat Hematol Oncol, Konya, Turkey
  • 5. Istanbul Univ, Cerrahpasa Med Fac, Dept Pediat Hematol, Istanbul, Turkey
  • 6. Marmara Univ, Fac Med, Dept Pediat Hematol, Istanbul, Turkey
  • 7. Istanbul Univ, Istanbul Fac Med, Dept Pediat Hematol Oncol, Istanbul, Turkey
  • 8. Dr Behcet Uz Children Res & Training Hosp, Dept Pediat Hematol Oncol, Izmir, Turkey
  • 9. Ege Univ, Fac Med, Dept Pediat Genet, Izmir, Turkey
  • 10. Ege Univ, Fac Med, Dept Med Genet, Izmir, Turkey
  • 11. Med Pk Goztepe Hosp, Pediat Bone Marrow Transplantat Unit, Istanbul, Turkey
  • 12. Akdeniz Univ, Med Sch, Dept Pediat Hematol, Antalya, Turkey
  • 13. Marmara Univ, Fac Med, Dept Pediat Allergy & Immunol, Istanbul, Turkey
  • 14. Cukurova Univ, Fac Med, Dept Pediat Hematol, Adana, Turkey

Description

Background Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. Method Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. Results The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (+/- mean standard error) follow-up period was 129.7 +/- 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. Conclusion In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.

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