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WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4.

Publication ,  Journal Article
Liu, Q; Chen, H; Ojode, T; Gao, X; Anaya-O'Brien, S; Turner, NA; Ulrick, J; DeCastro, R; Kelly, C; Cardones, AR; Gold, SH; Hwang, EI ...
Published in: Blood
July 5, 2012

WHIM syndrome is a rare, autosomal dominant, immunodeficiency disorder so-named because it is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (defective neutrophil egress from the BM). Gain-of-function mutations that truncate the C-terminus of the chemokine receptor CXCR4 by 10-19 amino acids cause WHIM syndrome. We have identified a family with autosomal dominant inheritance of WHIM syndrome that is caused by a missense mutation in CXCR4, E343K (1027G → A). This mutation is also located in the C-terminal domain, a region responsible for negative regulation of the receptor. Accordingly, like CXCR4(R334X), the most common truncation mutation in WHIM syndrome, CXCR4(E343K) mediated approximately 2-fold increased signaling in calcium flux and chemotaxis assays relative to wild-type CXCR4; however, CXCR4(E343K) had a reduced effect on blocking normal receptor down-regulation from the cell surface. Therefore, in addition to truncating mutations in the C-terminal domain of CXCR4, WHIM syndrome may be caused by a single charge-changing amino acid substitution in this domain, E343K, that results in increased receptor signaling.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

July 5, 2012

Volume

120

Issue

1

Start / End Page

181 / 189

Location

United States

Related Subject Headings

  • Warts
  • Receptors, CXCR4
  • Protein Structure, Tertiary
  • Primary Immunodeficiency Diseases
  • Phenotype
  • Pedigree
  • Molecular Sequence Data
  • Male
  • Leukopenia
  • K562 Cells
 

Citation

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Liu, Q., Chen, H., Ojode, T., Gao, X., Anaya-O’Brien, S., Turner, N. A., … McDermott, D. H. (2012). WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4. Blood, 120(1), 181–189. https://doi.org/10.1182/blood-2011-12-395608
Liu, Qian, Haoqian Chen, Teresa Ojode, Xiangxi Gao, Sandra Anaya-O’Brien, Nicholas A. Turner, Jean Ulrick, et al. “WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4.Blood 120, no. 1 (July 5, 2012): 181–89. https://doi.org/10.1182/blood-2011-12-395608.
Liu Q, Chen H, Ojode T, Gao X, Anaya-O’Brien S, Turner NA, et al. WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4. Blood. 2012 Jul 5;120(1):181–9.
Liu, Qian, et al. “WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4.Blood, vol. 120, no. 1, July 2012, pp. 181–89. Pubmed, doi:10.1182/blood-2011-12-395608.
Liu Q, Chen H, Ojode T, Gao X, Anaya-O’Brien S, Turner NA, Ulrick J, DeCastro R, Kelly C, Cardones AR, Gold SH, Hwang EI, Wechsler DS, Malech HL, Murphy PM, McDermott DH. WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4. Blood. 2012 Jul 5;120(1):181–189.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

July 5, 2012

Volume

120

Issue

1

Start / End Page

181 / 189

Location

United States

Related Subject Headings

  • Warts
  • Receptors, CXCR4
  • Protein Structure, Tertiary
  • Primary Immunodeficiency Diseases
  • Phenotype
  • Pedigree
  • Molecular Sequence Data
  • Male
  • Leukopenia
  • K562 Cells