Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: Review of all reported cases and development of a clinical diagnostic paradigm

Julie A. Jaffray, W. Beau Mitchell, Merlin Nithya Gnanapragasam, Surya V. Seshan, Xinhuo Guo, Connie M. Westhoff, James J. Bieker, Deepa G. Manwani

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

KLF1 is an erythroid specific transcription factor that is involved in erythroid lineage commitment, globin switching and terminal red blood cell maturation. Various mutations of KLF1 have been identified in humans, which have led to both benign and pathological phenotypes. The E325K mutation, within the second zinc finger of the KLF1 gene, has been shown to cause a new form of congenital dyserythropoietic anemia (CDA) now labeled as CDA type IV. We report the fourth documented case of this mutation, and propose a clinical diagnostic model to better identify this disease in other patients. Our patient is a Taiwanese child who presented to us at 8. years of age with severe hemolytic anemia, splenomegaly, elevated fetal hemoglobin (HbF), iron overload, and dyserythropoiesis in the bone marrow. KLF1 sequence analysis revealed a G-to-A transition in one allele of exon 3, which resulted in the substitution of a glutamate 325 by a lysine. Flow cytometry analysis revealed decreased protein expression of CD44 on the red blood cells, and decreased red blood cell deformability as measured using an ektacytometer. Blood typing revealed his red blood cells to be Co(a-b-), In(b-), LW(ab-) and Lu(b. +), even though DNA testing predicted that he would be Co(a + b-) and LW(a + b-). This newly discovered CDA combines features of a hemoglobinopathy, RBC membrane defect and hereditary persistence of HbF (HPFH) which are not seen in the previous types of CDA. Increased awareness of this phenotype may improve the more prompt and accurate diagnosis of these patients.

Original languageEnglish (US)
Pages (from-to)71-75
Number of pages5
JournalBlood Cells, Molecules, and Diseases
Volume51
Issue number2
DOIs
StatePublished - Aug 2013

Fingerprint

Congenital Dyserythropoietic Anemia
Transcription Factors
Erythrocytes
Mutation
Blood Grouping and Crossmatching
Phenotype
Fetal Hemoglobin
Hemoglobinopathies
Iron Overload
Globins
Hemolytic Anemia
Splenomegaly
Zinc Fingers
Lysine
Sequence Analysis
Glutamic Acid
Exons
Flow Cytometry
Bone Marrow
Alleles

Keywords

  • Colton blood group
  • Congenital dyserythropoietic anemia
  • E325K mutation
  • KLF-1

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology
  • Cell Biology

Cite this

Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin : Review of all reported cases and development of a clinical diagnostic paradigm. / Jaffray, Julie A.; Mitchell, W. Beau; Gnanapragasam, Merlin Nithya; Seshan, Surya V.; Guo, Xinhuo; Westhoff, Connie M.; Bieker, James J.; Manwani, Deepa G.

In: Blood Cells, Molecules, and Diseases, Vol. 51, No. 2, 08.2013, p. 71-75.

Research output: Contribution to journalArticle

Jaffray, Julie A. ; Mitchell, W. Beau ; Gnanapragasam, Merlin Nithya ; Seshan, Surya V. ; Guo, Xinhuo ; Westhoff, Connie M. ; Bieker, James J. ; Manwani, Deepa G. / Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin : Review of all reported cases and development of a clinical diagnostic paradigm. In: Blood Cells, Molecules, and Diseases. 2013 ; Vol. 51, No. 2. pp. 71-75.
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