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Familial occurrence of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome.

Siedlar M, Rudzki Z, Strach M, Trzyna E, Pituch-Noworolska A, Błaut-Szlósarczyk A, Bukowska-Strakova K, Lenart M, Grodzicki T, Zembala M - Arch. Immunol. Ther. Exp. (Warsz.) (2008)

Bottom Line: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage.Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663 Cracow, Poland. misiedla@cyf-kr.edu.pl

ABSTRACT

Introduction: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder with an autosomal-dominant pattern of inheritance and low fatality rate but significant lifelong morbidity.

Materials and methods: A 27-year-old mother of two children has been suffering from severe neutropenia and recurrent infections with the diagnosis of sporadic WHIM syndrome established by sequencing the CXCR4 gene and the finding of a heterozygous 1000 C-->T nonsense mutation in the second CXCR4 exon. The first child was an apparently healthy boy delivered at full term. Umbilical cord blood cells were obtained for genetic analysis. Peripheral blood cells were also analyzed at 8 months of life. Both analyses revealed the same mutation as that of his mother. The child was in a good condition, manifesting neutropenia without infections until 11 months of life. He subsequently developed pneumonia requiring a more aggressive treatment. After that, the regular substitution of immunoglobulins (IVIGs) and G-CSF has been preventing serious infections. Six months ago the second boy was delivered who also demonstrated neutropenia without severe infections. Genetic studies using cord blood and also peripheral blood cells in the fourth month showed an identical mutation of the CXCR4 gene as in his mother. Moreover, the mother and her first son demonstrated monocytopenia.

Results: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage. Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.

Conclusions: This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

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Related in: MedlinePlus

Analysis of the CD14+CD16+ and CD14++CD16− subpopulations of monocytes. The gate was first set on a “CD45 vs. Side Scatter” dot plot around the CD45-positive monocytes and adjacent lymphocytes (data not shown). These cells were then gated to exclude the CD14-HLA-DR− NK cell population (A) and finally analyzed with respect to CD14 and CD16 antigen expression (B). Analyses of a typical healthy adult (B) and healthy child (D) as well as the mother with WHIM syndrome (C) and her first son (E) are shown.
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Fig3: Analysis of the CD14+CD16+ and CD14++CD16− subpopulations of monocytes. The gate was first set on a “CD45 vs. Side Scatter” dot plot around the CD45-positive monocytes and adjacent lymphocytes (data not shown). These cells were then gated to exclude the CD14-HLA-DR− NK cell population (A) and finally analyzed with respect to CD14 and CD16 antigen expression (B). Analyses of a typical healthy adult (B) and healthy child (D) as well as the mother with WHIM syndrome (C) and her first son (E) are shown.

Mentions: A low number of “proinflammatory” CD14+CD16+ monocytes in the mother (1 cell/µl; Fig. 3C) and in the first son (10 cells/µl; Fig. 3E) was also observed. The numbers of “classical” CD14++CD16− monocytes were also decreased in both patients (59 cells/µl and 110 cells/µl, respectively; Figs. 3C, E). In our material the numbers of CD14+CD16+ monocytes in healthy adult volunteers (over 18 years old) were 66±31 cells/µl (n=17) and in children 58±34 cells/µl (n=60). The numbers of CD14++CD16− monocytes were, respectively, 549±233 cells/µl and 430±158 cells/µl. The plots in Figs. 3B and 3D are representative of age-matched blood donors without immunodeficiency.Fig. 3


Familial occurrence of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome.

Siedlar M, Rudzki Z, Strach M, Trzyna E, Pituch-Noworolska A, Błaut-Szlósarczyk A, Bukowska-Strakova K, Lenart M, Grodzicki T, Zembala M - Arch. Immunol. Ther. Exp. (Warsz.) (2008)

Analysis of the CD14+CD16+ and CD14++CD16− subpopulations of monocytes. The gate was first set on a “CD45 vs. Side Scatter” dot plot around the CD45-positive monocytes and adjacent lymphocytes (data not shown). These cells were then gated to exclude the CD14-HLA-DR− NK cell population (A) and finally analyzed with respect to CD14 and CD16 antigen expression (B). Analyses of a typical healthy adult (B) and healthy child (D) as well as the mother with WHIM syndrome (C) and her first son (E) are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2805795&req=5

Fig3: Analysis of the CD14+CD16+ and CD14++CD16− subpopulations of monocytes. The gate was first set on a “CD45 vs. Side Scatter” dot plot around the CD45-positive monocytes and adjacent lymphocytes (data not shown). These cells were then gated to exclude the CD14-HLA-DR− NK cell population (A) and finally analyzed with respect to CD14 and CD16 antigen expression (B). Analyses of a typical healthy adult (B) and healthy child (D) as well as the mother with WHIM syndrome (C) and her first son (E) are shown.
Mentions: A low number of “proinflammatory” CD14+CD16+ monocytes in the mother (1 cell/µl; Fig. 3C) and in the first son (10 cells/µl; Fig. 3E) was also observed. The numbers of “classical” CD14++CD16− monocytes were also decreased in both patients (59 cells/µl and 110 cells/µl, respectively; Figs. 3C, E). In our material the numbers of CD14+CD16+ monocytes in healthy adult volunteers (over 18 years old) were 66±31 cells/µl (n=17) and in children 58±34 cells/µl (n=60). The numbers of CD14++CD16− monocytes were, respectively, 549±233 cells/µl and 430±158 cells/µl. The plots in Figs. 3B and 3D are representative of age-matched blood donors without immunodeficiency.Fig. 3

Bottom Line: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage.Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663 Cracow, Poland. misiedla@cyf-kr.edu.pl

ABSTRACT

Introduction: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder with an autosomal-dominant pattern of inheritance and low fatality rate but significant lifelong morbidity.

Materials and methods: A 27-year-old mother of two children has been suffering from severe neutropenia and recurrent infections with the diagnosis of sporadic WHIM syndrome established by sequencing the CXCR4 gene and the finding of a heterozygous 1000 C-->T nonsense mutation in the second CXCR4 exon. The first child was an apparently healthy boy delivered at full term. Umbilical cord blood cells were obtained for genetic analysis. Peripheral blood cells were also analyzed at 8 months of life. Both analyses revealed the same mutation as that of his mother. The child was in a good condition, manifesting neutropenia without infections until 11 months of life. He subsequently developed pneumonia requiring a more aggressive treatment. After that, the regular substitution of immunoglobulins (IVIGs) and G-CSF has been preventing serious infections. Six months ago the second boy was delivered who also demonstrated neutropenia without severe infections. Genetic studies using cord blood and also peripheral blood cells in the fourth month showed an identical mutation of the CXCR4 gene as in his mother. Moreover, the mother and her first son demonstrated monocytopenia.

Results: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage. Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.

Conclusions: This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

Show MeSH
Related in: MedlinePlus