Tags

Type your tag names separated by a space and hit enter

Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis.
Blood Cells Mol Dis. 2016 10; 61:4-9.BC

Abstract

Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are heterogeneous red blood cell (RBC) membrane disorders that result from mutations in the genes encoding α-spectrin (SPTA1), β-spectrin (SPTB), or protein 4.1R (EPB41). The resulting defects alter the horizontal cytoskeletal associations and affect RBC membrane stability and deformability causing shortened RBC survival. The clinical diagnosis of HE and HPP relies on identifying characteristic RBC morphology on peripheral blood smear and specific membrane biomechanical properties using osmotic gradient ektacytometry. However, this phenotypic diagnosis may not be readily available in patients requiring frequent transfusions, and does not predict disease course or severity. Using Next-Generation sequencing, we identified the causative genetic mutations in fifteen patients with clinically suspected HE or HPP and correlated the identified mutations with the clinical phenotype and ektacytometry profile. In addition to identifying three novel mutations, gene sequencing confirmed and, when the RBC morphology was not evaluable, identified the diagnosis. Moreover, genotypic differences justified the phenotypic differences within families with HE/HPP.

Authors+Show Affiliations

Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: omar.niss@cchmc.org.Emory University School of Medicine, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.Thalassemia and Genetic Center, Dubai, UAE.SUNY Upstate Medical University, Syracuse, NY, USA.Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.Emory University School of Medicine, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.College of Nursing, University of Cincinnati, Cincinnati, OH, USA.Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27667160

Citation

Niss, Omar, et al. "Genotype-phenotype Correlations in Hereditary Elliptocytosis and Hereditary Pyropoikilocytosis." Blood Cells, Molecules & Diseases, vol. 61, 2016, pp. 4-9.
Niss O, Chonat S, Dagaonkar N, et al. Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis. Blood Cells Mol Dis. 2016;61:4-9.
Niss, O., Chonat, S., Dagaonkar, N., Almansoori, M. O., Kerr, K., Rogers, Z. R., McGann, P. T., Quarmyne, M. O., Risinger, M., Zhang, K., & Kalfa, T. A. (2016). Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis. Blood Cells, Molecules & Diseases, 61, 4-9. https://doi.org/10.1016/j.bcmd.2016.07.003
Niss O, et al. Genotype-phenotype Correlations in Hereditary Elliptocytosis and Hereditary Pyropoikilocytosis. Blood Cells Mol Dis. 2016;61:4-9. PubMed PMID: 27667160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis. AU - Niss,Omar, AU - Chonat,Satheesh, AU - Dagaonkar,Neha, AU - Almansoori,Marya O, AU - Kerr,Karol, AU - Rogers,Zora R, AU - McGann,Patrick T, AU - Quarmyne,Maa-Ohui, AU - Risinger,Mary, AU - Zhang,Kejian, AU - Kalfa,Theodosia A, Y1 - 2016/07/17/ PY - 2016/02/19/received PY - 2016/07/15/revised PY - 2016/07/15/accepted PY - 2016/9/27/entrez PY - 2016/9/27/pubmed PY - 2018/1/13/medline KW - Elliptocytosis KW - Hemolytic anemia KW - Mutation KW - Pyropoikilocytosis KW - Red blood cell membrane SP - 4 EP - 9 JF - Blood cells, molecules & diseases JO - Blood Cells Mol. Dis. VL - 61 N2 - Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are heterogeneous red blood cell (RBC) membrane disorders that result from mutations in the genes encoding α-spectrin (SPTA1), β-spectrin (SPTB), or protein 4.1R (EPB41). The resulting defects alter the horizontal cytoskeletal associations and affect RBC membrane stability and deformability causing shortened RBC survival. The clinical diagnosis of HE and HPP relies on identifying characteristic RBC morphology on peripheral blood smear and specific membrane biomechanical properties using osmotic gradient ektacytometry. However, this phenotypic diagnosis may not be readily available in patients requiring frequent transfusions, and does not predict disease course or severity. Using Next-Generation sequencing, we identified the causative genetic mutations in fifteen patients with clinically suspected HE or HPP and correlated the identified mutations with the clinical phenotype and ektacytometry profile. In addition to identifying three novel mutations, gene sequencing confirmed and, when the RBC morphology was not evaluable, identified the diagnosis. Moreover, genotypic differences justified the phenotypic differences within families with HE/HPP. SN - 1096-0961 UR - https://www.unboundmedicine.com/medline/citation/27667160/Genotype_phenotype_correlations_in_hereditary_elliptocytosis_and_hereditary_pyropoikilocytosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1079-9796(16)30088-2 DB - PRIME DP - Unbound Medicine ER -