Identification of Novel Mutations in Children with Hereditary Spherocytosis by Targeted Exome Sequencing: A Single Center Experience
Abstract
Aim: Hereditary spherocytosis (HS) is a prevalent cause of congenital hemolytic anemia in Northern
Europeans. It is characterized by spherocytes resulting from defects in the erythrocyte structural
membrane proteins spectrin and ankyrin. To date, more than five candidate genes, including ANK1,
SPTB, SPTA1, SLC4A1, and EPB42 have been linked to HS. Here, we aim to investigate the presence
of novel as well as known mutations in eight Turkish children with clinically suspected HS.
Material and Methods: We presented the clinical features of the patients and identified the causative
gene variants using targeted exome sequencing. Eight children who were clinically suspected of having
HS enrolled in this study. A family and medical history, clinical examination, relevant laboratory test
results, osmotic fragility test (OFT), and genetic results were evaluated.
Results: Six causative variants, including three ANK1 variants, two SPTB variants and one SLC4A1
variant were detected. All these mutations were novel variants. ANK1 and SPTB are the most common
mutant genes in children with HS.
Conclusion: This study expanded the mutation spectrum of ANK1, SPTB and SLC4A1. This is the first
study to determine the genetic and clinical characteristics of children with HS in Turkey.
References
- 1. Huq S, Pietroni MA, Rahman H, Alam MT. Hereditary spherocytosis. J Health Popul Nutr. 2010;28(1):107-9.
- 2. Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King MJ. Guidelines for the diagnosis and management of hereditary spherocytosis. Br J Haematol. 2004;126(4):455-74.
- 3. Hao L, Li S, Ma D, Chen S, Zhang B, Xiao D, Zhang J, Jiang N, Jiang S, Ma J. Two novel ANK1 loss-of-function mutations in Chinese families with hereditary spherocytosis. J Cell Mol Med. 2019 Jun;23(6):4454-4463.
- 4. An X, Mohandas N. Disorders of red cell membrane. Br J Haematol. 2008;141(3):367-75.
Hedeflenmiş Ekzom Dizilimi ile Kalıtsal Sferositozlu Çocuklarda Yeni Mutasyonların Belirlenmesi: Tek Merkez Deneyimi
Abstract
Amaç: Kalıtsal sferositoz (HS), Kuzey Avrupalılarda konjenital hemolitik aneminin yaygın bir nedenidir.
Eritrosit yapısal membran proteinleri spektrin ve ankirin’deki kusurlardan kaynaklanan sferositlerle
karakterizedir. Bugüne kadar, ANK1, SPTB, SPTA1, SLC4A1 ve EPB42 dahil olmak üzere beşten fazla
aday gen, HS ile ilişkilendirilmiştir. Burada, klinik olarak HS şüphesi olan sekiz Türk çocuğunda bilinen
ve yeni mutasyonların varlığını araştırmayı amaçladık.
Gereç ve Yöntemler: Hastaların klinik özelliklerini sunduk ve hedeflenen ekzom dizilimi kullanarak
nedensel gen varyantlarını belirledik. Klinik olarak HS olduğundan şüphelenilen sekiz çocuk bu
çalışmaya alındı. Aile ve tıbbi öykü, klinik muayene, ilgili laboratuvar test sonuçları, ozmotik frajilite testi
ve genetik sonuçlar değerlendirildi.
Bulgular: Üç ANK1 varyantı, iki SPTB varyantı ve bir SLC4A1 varyantı dahil olmak üzere 6 nedensel
varyant tespit edildi. Bütün bu mutasyonlar yeni varyantlardı. ANK1 ve SPTB, HS’li çocuklarda en sık
görülen mutant genlerdir.
Sonuç: Bu çalışma, ANK1, SPTB ve SLC4A1 genlerinin mutasyon spektrumunu genişletti. Bu,
Türkiye’de HS’li çocukların genetik ve klinik özelliklerini belirleyen ilk çalışmadır.
References
- 1. Huq S, Pietroni MA, Rahman H, Alam MT. Hereditary spherocytosis. J Health Popul Nutr. 2010;28(1):107-9.
- 2. Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King MJ. Guidelines for the diagnosis and management of hereditary spherocytosis. Br J Haematol. 2004;126(4):455-74.
- 3. Hao L, Li S, Ma D, Chen S, Zhang B, Xiao D, Zhang J, Jiang N, Jiang S, Ma J. Two novel ANK1 loss-of-function mutations in Chinese families with hereditary spherocytosis. J Cell Mol Med. 2019 Jun;23(6):4454-4463.
- 4. An X, Mohandas N. Disorders of red cell membrane. Br J Haematol. 2008;141(3):367-75.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Research Article |
| Authors | |
| Publication Date | December 27, 2022 |
| Acceptance Date | December 16, 2022 |
| Published in Issue | Year 2022 Volume: 6 Issue: 3 |
