Premium
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
Author(s) -
Yılmaz Karapınar Deniz,
Patıroğlu Türkan,
Metin Ayşe,
Çalışkan Ümran,
Celkan Tiraje,
Yılmaz Barış,
Karakaş Zeynep,
Karapınar Tuba H.,
Akıncı Burcu,
Özkınay Ferda,
Onay Hüseyin,
Yeşilipek Mehmet Akif,
Akar Himmet Haluk,
Tüysüz Gülen,
Tokgöz Hüseyin,
Özdemir Gül Nihal,
Aslan Kıykım Ayça,
Karaman Serap,
Kılınç Yurdanur,
Oymak Yeşim,
Küpesiz Alphan,
Olcay Lale,
Keskin Yıldırım Zuhal,
Aydoğan Gönül,
Gökçe Müge,
İleri Talia,
Aral Yusuf Ziya,
Bay Ali,
Atabay Berna,
Kaya Zuhre,
Söker Murat,
Özdemir Karadaş Nihal,
Özbek Uğur,
Özsait Selçuk Bilge,
Özdemir Hamiyet Hekimci,
Uygun Vedat,
Tezcan Karasu Gülsün,
Yılmaz Şebnem
Publication year - 2019
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.27923
Subject(s) - congenital neutropenia , medicine , neutropenia , cyclic neutropenia , pediatrics , mutation , consanguinity , genetics , gene , chemotherapy , biology
Abstract 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.