Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis

Omar Niss, Satheesh Chonat, Neha Dagaonkar, Marya O. Almansoori, Karol Kerr, Zora R. Rogers, Patrick T. McGann, Maa Ohui Quarmyne, Mary Risinger, Kejian Zhang, Theodosia A. Kalfa

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4-9
Number of pages6
JournalBlood Cells, Molecules, and Diseases
Volume61
DOIs
StatePublished - Oct 1 2016

Fingerprint

Hereditary Elliptocytosis
Genetic Association Studies
Erythrocytes
Spectrin
Mutation
Cell Membrane
Genes
Cell Survival
Hereditary Pyropoikilocytosis
Phenotype
Membranes
Proteins

Keywords

  • Elliptocytosis
  • Hemolytic anemia
  • Mutation
  • Pyropoikilocytosis
  • Red blood cell membrane

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Hematology
  • Cell Biology

Cite this

Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis. / Niss, Omar; Chonat, Satheesh; Dagaonkar, Neha; Almansoori, Marya O.; Kerr, Karol; Rogers, Zora R.; McGann, Patrick T.; Quarmyne, Maa Ohui; Risinger, Mary; Zhang, Kejian; Kalfa, Theodosia A.

In: Blood Cells, Molecules, and Diseases, Vol. 61, 01.10.2016, p. 4-9.

Research output: Contribution to journalArticle

Niss, O, Chonat, S, Dagaonkar, N, Almansoori, MO, Kerr, K, Rogers, ZR, McGann, PT, Quarmyne, MO, Risinger, M, Zhang, K & Kalfa, TA 2016, 'Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis', Blood Cells, Molecules, and Diseases, vol. 61, pp. 4-9. https://doi.org/10.1016/j.bcmd.2016.07.003
Niss, Omar ; Chonat, Satheesh ; Dagaonkar, Neha ; Almansoori, Marya O. ; Kerr, Karol ; Rogers, Zora R. ; McGann, Patrick T. ; Quarmyne, Maa Ohui ; Risinger, Mary ; Zhang, Kejian ; Kalfa, Theodosia A. / Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis. In: Blood Cells, Molecules, and Diseases. 2016 ; Vol. 61. pp. 4-9.
@article{7f518ff88d14456aa2d43de4b6d55735,
title = "Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis",
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.",
keywords = "Elliptocytosis, Hemolytic anemia, Mutation, Pyropoikilocytosis, Red blood cell membrane",
author = "Omar Niss and Satheesh Chonat and Neha Dagaonkar and Almansoori, {Marya O.} and Karol Kerr and Rogers, {Zora R.} and McGann, {Patrick T.} and Quarmyne, {Maa Ohui} and Mary Risinger and Kejian Zhang and Kalfa, {Theodosia A.}",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.bcmd.2016.07.003",
language = "English (US)",
volume = "61",
pages = "4--9",
journal = "Blood Cells, Molecules, and Diseases",
issn = "1079-9796",
publisher = "Academic Press Inc.",

}

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.

PY - 2016/10/1

Y1 - 2016/10/1

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.

AB - 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.

KW - Elliptocytosis

KW - Hemolytic anemia

KW - Mutation

KW - Pyropoikilocytosis

KW - Red blood cell membrane

UR - http://www.scopus.com/inward/record.url?scp=84979684858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979684858&partnerID=8YFLogxK

U2 - 10.1016/j.bcmd.2016.07.003

DO - 10.1016/j.bcmd.2016.07.003

M3 - Article

C2 - 27667160

AN - SCOPUS:84979684858

VL - 61

SP - 4

EP - 9

JO - Blood Cells, Molecules, and Diseases

JF - Blood Cells, Molecules, and Diseases

SN - 1079-9796

ER -