Red cell membrane disorders

Narla, Jyothsna; Mohandas, Narla

doi:10.1111/ijlh.12657

Cited by 125 publications

(111 citation statements)

References 38 publications

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“…HS is a highly heterogeneous disorder, due to deficiency or dysfunctioning of the proteins involved in maintaining the integrity and flexibility of red cell membrane which hampers membrane surface area and thereby leads to the formation of a spheroid, osmotically fragile cells (Narla & Mohandas, ). Clinically, HS is suspected with the finding of jaundice, hepatosplenomegaly, anemia with the presence of spherocytes on the peripheral blood smear of a patient.…”

Section: Discussionmentioning

confidence: 99%

“…The red cell membrane skeleton is a dynamic system and has many important antigenic, transport, and mechanical functions. It provides the erythrocyte its flexibility, durability, and density for undergoing cellular deformations during repeated passage in its 120‐days lifespan (Narla & Mohandas, ; Samuel & Lux, ). The biconcave discoid shape of the erythrocyte is maintained by skeletal proteins, which mainly include ankyrin, α‐spectrin, β‐spectrin, anion exchanger channel protein (band‐3 protein), Protein 4.1 and 4.2, and actin.…”

Section: Introductionmentioning

confidence: 99%

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Applications of imaging flow cytometry in the diagnostic assessment of red cell membrane disorders

Dalal

Devendra

et al. 2019

Cytometry Part B Clinical

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Background: Red cell membranopathies refers to phenotypically and morphologically heterogeneous disorders. High throughput imaging flow cytometry (IFC) combines the speed, sensitivity, and phenotyping abilities of flow cytometry with the detailed imagery and functional insights of microscopy to produce high content image analysis with quantitative analysis. We have evaluated the applications of IFC to examine both the morphology as well as fluorescence signal intensity in red cell membranopathies.Methods: Fluorescence intensity of eosin-5-maleimide (EMA) labeled red cells was measured for diagnosis of RBC membrane protein defect on Amnis ImageStreamX followed by Image analysis on IDEAS software to study features such as circularity and shape ratio.Results: The hereditary spherocytosis (HS) group showed significantly decreased MFI (52,800 ± 9,100) than normal controls (81,100 ± 4,700) (p < .05) whereas non-HS showed 78,300 ± 9,900. The shape ratio of hereditary elliptocytosis (HE) was significantly higher (43.8%) than normal controls (14.6%). The circularity score is higher in HS (64.15%) than the normal controls (44.3%) whereas the circularity score was very less in HE (10%) due to the presence of elliptocytes. Conclusions:The advantages of the IFC over standard flow cytometry is its ability to provide high-content image analysis and measurement of parameters such as circularity and shape ratio allow discriminating red cell membranopathies (HS and HE) due to variations in shape and size. It could be a single, effective, and rapid IFC test for detection and differentiation of red cell membrane disorders in hematology laboratories where an IFC is available. K E Y W O R D S hereditary spherocytosis, imaging flow cytometry, red blood cell

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Applications of imaging flow cytometry in the diagnostic assessment of red cell membrane disorders

Dalal

Devendra

et al. 2019

Cytometry Part B Clinical

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“…The red cell plasma membrane ensures the maintenance of osmolarity and deformability. Indeed, modification of either osmolarity or protein composition can reduce the RBC lifespan (Narla & Mohandas, ; Caulier et al , ). Several proteomic studies have shed light on the composition of the red cell plasma membrane.…”

Section: Updates On the Composition Of The Red Cell Plasma Membranementioning

confidence: 99%

“…The lipid bilayer contains phospholipids, cholesterol and integral transmembrane proteins that are bound to the skeleton through linker proteins (Lux, ). Cholesterol regulates the fluidity of the plasma membrane and is present in both leaflet faces, whereas phospholipids show an asymmetric distribution that is maintained by proteins termed “scramblases” and “flippases” (Narla & Mohandas, ). ATP11C and phospholipid scramblase 1 are major representatives of these classes of proteins (Arashiki et al , ,; Takatsu et al , ).…”

Section: Updates On the Composition Of The Red Cell Plasma Membranementioning

confidence: 99%

Advances in understanding the pathogenesis of red cell membrane disorders

2019

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Summary Hereditary erythrocyte membrane disorders are caused by mutations in genes encoding various transmembrane or cytoskeletal proteins of red blood cells. The main consequences of these genetic alterations are decreased cell deformability and shortened erythrocyte survival. Red blood cell membrane defects encompass a heterogeneous group of haemolytic anaemias caused by either (i) altered membrane structural organisation (hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and Southeast Asian ovalocytosis) or (ii) altered membrane transport function (overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis or xerocytosis, familial pseudohyperkalaemia and cryohydrocytosis). Herein we provide a comprehensive review of the recent literature on the molecular genetics of erythrocyte membrane defects and their reported clinical consequences. We also describe the effect of low‐expression genetic variants on the high inter‐ and intra‐familial phenotype variability of erythrocyte structural defects.

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“…Among Chinese populations, the incidence of HS is approximately 1/ 100000 [3]. Typical clinical manifestations of HS include anaemia, haemolysis, jaundice, splenomegaly and gallstones [4]. However, clinical presentations vary widely, ranging from nearly asymptomatic to transfusion-dependent or severe life-threatening anaemia, and can be aggravated by infection, pregnancy, and sudden haemorrhage, among others [5].…”

Section: Introductionmentioning

confidence: 99%

Targeted next-generation sequencing identified a novel ANK1 mutation associated with hereditary spherocytosis in a Chinese family

Sun

Xie

et al. 2019

Hematology

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2019) Targeted next-generation sequencing identified a novel ANK1 mutation associated with hereditary spherocytosis in a Chinese family, Hematology, 24:1, 583-587, ABSTRACTObjectives: Hereditary spherocytosis (HS) represents a group of congenital diseases characterized by sphere-shaped erythrocytes on peripheral blood smears. The typical clinical manifestations of HS include haemolysis, jaundice, splenomegaly, and gallstones. Ankyrin1, encoded by the ANK1 gene, is the predominant protein in red blood cells. Defects in ankyrin1 lead to a decrease in erythrocyte surface area, a spherical shape of erythrocytes and, in particular, loss of membrane elasticity and mechanical stability. The purpose of this study was to investigate a Chinese family with HS to determine the causative gene mutation and explore the genotype-phenotype correlation. Methods: A 4-year-old boy was diagnosed with HS based on typical clinical features. In addition, his father had a high possibility of HS. Targeted next-generation sequencing (NGS) followed by Sanger sequencing was performed in the proband and his parents. Results: One mutation in the ANK1 gene was recognized. c1801-1G > C in exon 17, which leads to splicing defects, was detected. To confirm the c1801-1G > C variant, samples from the proband and his parents were analysed by Sanger sequencing, and Sanger verification showed that this mutation was inherited from the father. Conclusion: The present study confirmed that a novel mutation in ANK1 may be causative of HS, which plays an important role in expanding the mutational spectrum of ANK1 mutations. This may contribute to accurate genetic counselling. And it is helpful for understanding the correlation of the genotype and phenotype.

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Red cell membrane disorders

Cited by 125 publications

References 38 publications

Applications of imaging flow cytometry in the diagnostic assessment of red cell membrane disorders

Applications of imaging flow cytometry in the diagnostic assessment of red cell membrane disorders

Advances in understanding the pathogenesis of red cell membrane disorders

Targeted next-generation sequencing identified a novel ANK1 mutation associated with hereditary spherocytosis in a Chinese family

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