Ann Lab Med.  2017 Sep;37(5):446-449. 10.3343/alm.2017.37.5.446.

WHIM Syndrome With a Novel CXCR4 Variant in a Korean Child

• Shin DW
• Park SN
• Kim SM
• Im K
• Kim JA
• Hong KT
• Choi JY
• Hong CR
• Park KD
• Shin HY
• Kang HJ
• Kim HK
• Lee DS

• KMID: 2383923
• DOI: http://doi.org/10.3343/alm.2017.37.5.446

Abstract

No abstract available.

MeSH Terms

Child*
Humans

Figure

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  Fig. 1 WBC and ANC results according to the patient's age and clinical events.Abbreviations: CBC, complete blood count; WBC, white blood cell; ANC, absolute neutrophil count; G-CSF, granulocyte colony stimulating factor; BM, bone marrow; y, year(s); m, month(s).

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  Fig. 2 Results of bone marrow examination and Sanger sequencing of the CXCR4 gene. (A–F) Neutrophils with pyknotic nuclei, lobes separated by long strands of chromatin, and cytoplasmic vacuoles were observed (Wright Giemsa stain, ×1,000); (G) Marrow with hypercellularity and multifocal collections of mature neutrophils were observed (hematoxylin and eosin stain, ×200); (H) Anti-CXCR4 immunohistochemical stain showed an absence of CXCR4 surface protein; (I) A mouse spleen section was stained as a positive control for anti-CXCR4 stain (×400; Ab1670, Abcam, Cambridge, UK); (J) Chromatogram was obtained from Sanger sequencing of the CXCR4 gene (reference sequence: NM_003467.2). Reverse sequence reading from the 3′ end revealed the c.966_967delAG frameshift variant. Designation was based on the 3′ rule that the most 3′ position possible of the reference sequence is arbitrarily assigned to have been changed.

Reference

1. Pozzobon T, Goldoni G, Viola A, Molon B. CXCR4 signaling in health and disease. Immunol Lett. 2016; 177:6–15. PMID: 27363619.

2. Ana Rath, Stéphanie Nguengang Wakap, Samuel Demarest, Valérie Lanneau (Eds), Prevalence of rare diseases: Bibliographic data, Orphanet Report Series, Rare Diseases collection, November 2016, Number 1 : Diseases listed in alphabetical order. Updated on Nov 2016. http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf.

3. Kawai T, Malech HL. WHIM Syndrome: congenital immune deficiency disease. Curr Opin Hematol. 2009; 16:20–26. PMID: 19057201.

4. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis. 2011; 6:26. PMID: 21595885.

5. Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med. 2007; 13:587–596. PMID: 17435771.

6. Pavlasova G, Borsky M, Seda V, Cerna K, Osickova J, Doubek M, et al. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood. 2016; 128:1609–1613. PMID: 27480113.

7. Beaussant Cohen S, Fenneteau O, Plouvier E, Rohrlich PS, Daltroff G, Plantier I, et al. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry. Orphanet J Rare Dis. 2012; 7:71. PMID: 23009155.

8. Pawig L, Klasen C, Weber C, Bernhagen J, Noels H. Diversity and inter-connections in the CXCR4 chemokine receptor/ligand family: molecular perspectives. Front Immunol. 2015; 6:429. PMID: 26347749.

9. Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. The genomic landscape of Waldenström macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood. 2014; 123:1637–1646. PMID: 24366360.

10. Balabanian K, Lagane B, Pablos JL, Laurent L, Planchenault T, Verola O, et al. WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12. Blood. 2005; 105:2449–2457. PMID: 15536153.