دورية أكاديمية

The Spectrum of SPTA1-Associated Hereditary Spherocytosis

التفاصيل البيبلوغرافية
العنوان: The Spectrum of SPTA1-Associated Hereditary Spherocytosis
المؤلفون: Satheesh Chonat, Mary Risinger, Haripriya Sakthivel, Omar Niss, Jennifer A. Rothman, Loan Hsieh, Stella T. Chou, Janet L. Kwiatkowski, Eugene Khandros, Matthew F. Gorman, Donald T. Wells, Tamara Maghathe, Neha Dagaonkar, Katie G. Seu, Kejian Zhang, Wenying Zhang, Theodosia A. Kalfa
المصدر: Frontiers in Physiology, Vol 10 (2019)
بيانات النشر: Frontiers Media S.A., 2019.
سنة النشر: 2019
المجموعة: LCC:Physiology
مصطلحات موضوعية: SPTA1, α-spectrin, αLEPRA, hereditary spherocytosis, next generation sequencing, hemolytic anemia, Physiology, QP1-981
الوصف: Hereditary spherocytosis (HS) is the most common red blood cell (RBC) membrane disorder causing hereditary hemolytic anemia. Patients with HS have defects in the genes coding for ankyrin (ANK1), band 3 (SLC4A1), protein 4.2 (EPB42), and α (SPTA1) or β-spectrin (SPTB). Severe recessive HS is most commonly due to biallelic SPTA1 mutations. α-spectrin is produced in excess in normal erythroid cells, therefore SPTA1-associated HS ensues with mutations causing significant decrease of normal protein expression from both alleles. In this study, we systematically compared genetic, rheological, and protein expression data to the varying clinical presentation in eleven patients with SPTA1-associated HS. The phenotype of HS in this group of patients ranged from moderately severe to severe transfusion-dependent anemia and up to hydrops fetalis which is typically fatal if transfusions are not initiated before term delivery. The pathogenicity of the mutations could be corroborated by reduced SPTA1 mRNA expression in the patients’ reticulocytes. The disease severity correlated to the level of α-spectrin protein in their RBC cytoskeleton but was also affected by other factors. Patients carrying the low expression αLEPRA allele in trans to a null SPTA1 mutation were not all transfusion dependent and their anemia improved or resolved with partial or total splenectomy, respectively. In contrast, patients with near-complete or complete α-spectrin deficiency have a history of having been salvaged from fatal hydrops fetalis, either because they were born prematurely and started transfusions early or because they had intrauterine transfusions. They have suboptimal reticulocytosis or reticulocytopenia and remain transfusion dependent even after splenectomy; these patients require either lifetime transfusions and iron chelation or stem cell transplant. Comprehensive genetic and phenotypic evaluation is critical to provide accurate diagnosis in patients with SPTA1-associated HS and guide toward appropriate management.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1664-042X
Relation: https://www.frontiersin.org/article/10.3389/fphys.2019.00815/full; https://doaj.org/toc/1664-042X
DOI: 10.3389/fphys.2019.00815
URL الوصول: https://doaj.org/article/ad840012f1744b04820b5b66c13c0ebd
رقم الأكسشن: edsdoj.840012f1744b04820b5b66c13c0ebd
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1664042X
DOI:10.3389/fphys.2019.00815