The Spectrum of SPTA1-Associated Hereditary Spherocytosis

被引：40

作者：

Chonat, Satheesh ^{[1
,2
]}

Risinger, Mary ^{[3
]}

Sakthivel, Haripriya ^{[4
]}

Niss, Omar ^{[4
,5
]}

Rothman, Jennifer A. ^{[6
]}

Hsieh, Loan ^{[7
,8
]}

Chou, Stella T. ^{[9
,10
]}

Kwiatkowski, Janet L. ^{[9
,10
]}

Khandros, Eugene ^{[3
,10
]}

Gorman, Matthew F. ^{[11
]}

Wells, Donald T. ^{[12
]}

Maghathe, Tamara ^{[4
]}

Dagaonkar, Neha ^{[13
]}

Seu, Katie G. ^{[4
]}

Zhang, Kejian ^{[14
]}

Zhang, Wenying ^{[5
,15
]}

Kalfa, Theodosia A. ^{[4
,5
]}

机构：

[1] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA

[2] Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA

[3] Univ Cincinnati, Coll Nursing, Cincinnati, OH USA

[4] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA

[5] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45221 USA

[6] Duke Univ, Med Ctr, Durham, NC USA

[7] CHOC Childrens Hosp, Div Hematol, Orange, CA USA

[8] UC Irvine Med Ctr, Orange, CA USA

[9] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA

[10] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA

[11] Kaiser Permanente Santa Clara Med Ctr, Santa Clara, CA USA

[12] Dell Childrens Med Ctr, Austin, TX USA

[13] Columbia Univ, Genom Anal Facil, Inst Genom Med, New York, NY USA

[14] Coyote Biosci Co Ltd, San Jose, CA USA

[15] Cincinnati Childrens Hosp Med Ctr, Lab Genet & Genom, Div Human Genet, Cincinnati, OH 45229 USA

来源：

FRONTIERS IN PHYSIOLOGY | 2019年 / 10卷

基金：

美国国家卫生研究院;

关键词：

SPTA1; alpha-spectrin; alpha(LEPRA); hereditary spherocytosis; next generation sequencing; hemolytic anemia; hydrops fetalis; RED-CELL SPECTRIN; PROTEINS; ALPHA(LELY); DEFICIENCY; ALLELE;

D O I：

10.3389/fphys.2019.00815

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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 alpha (SPTA1) or beta-spectrin (SPTB). Severe recessive HS is most commonly due to biallelic SPTA1 mutations. alpha-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 u-spectrin protein in their RBC cytoskeleton but was also affected by other factors. Patients carrying the low expression alpha(LEPRA) 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 nearcomplete or complete alpha-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.

引用

页数：7

共 19 条

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