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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

Electropherograms of a portion of the CXCR4 gene's second exon of the mother and her children with WHIM syndrome show C→T heterozygosity at position 1000 in the cDNA sequence. Cord blood and peripheral blood collected from the children in the eighth (first son) and fourth (second son) months of life were taken for the study.
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Fig2: Electropherograms of a portion of the CXCR4 gene's second exon of the mother and her children with WHIM syndrome show C→T heterozygosity at position 1000 in the cDNA sequence. Cord blood and peripheral blood collected from the children in the eighth (first son) and fourth (second son) months of life were taken for the study.

Mentions: No mutations on the first exon of the CXCR4 gene were found. The studies concentrated on mutations on the second exon associated with changes in the intracellular tail domain essential for CXCR4 protein internalization [7]. The only observed change was C→T heterozygosity at the base corresponding to position 1000 in the CXCR4-DNA second exon sequence leading to a TGA stop codon. The observed nonsense mutation may cause shortening of the cytoplasmatic tail of CXCR4 protein. Such mutations were observed in the mother and in both her sons in the cells taken from cord and peripheral blood (Fig. 2). No such changes were found in the grandparents (data not shown). Neither the previously described [7] deletion of CT dinucleotide at position 1016–1017 nor a G→T change at position 1027 were found in the cDNA sequences. Forensic analysis of all 11 tested STR loci of the mother’s DNA revealed alleles specific to her parents, corroborating the notion of the spontaneous character of CXCR4 mutation in the mother, which had occurred in chromosome 2 of one of the parents of the proposita.


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)

Electropherograms of a portion of the CXCR4 gene's second exon of the mother and her children with WHIM syndrome show C→T heterozygosity at position 1000 in the cDNA sequence. Cord blood and peripheral blood collected from the children in the eighth (first son) and fourth (second son) months of life were taken for the study.
© Copyright Policy
Related In: Results  -  Collection

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

Fig2: Electropherograms of a portion of the CXCR4 gene's second exon of the mother and her children with WHIM syndrome show C→T heterozygosity at position 1000 in the cDNA sequence. Cord blood and peripheral blood collected from the children in the eighth (first son) and fourth (second son) months of life were taken for the study.
Mentions: No mutations on the first exon of the CXCR4 gene were found. The studies concentrated on mutations on the second exon associated with changes in the intracellular tail domain essential for CXCR4 protein internalization [7]. The only observed change was C→T heterozygosity at the base corresponding to position 1000 in the CXCR4-DNA second exon sequence leading to a TGA stop codon. The observed nonsense mutation may cause shortening of the cytoplasmatic tail of CXCR4 protein. Such mutations were observed in the mother and in both her sons in the cells taken from cord and peripheral blood (Fig. 2). No such changes were found in the grandparents (data not shown). Neither the previously described [7] deletion of CT dinucleotide at position 1016–1017 nor a G→T change at position 1027 were found in the cDNA sequences. Forensic analysis of all 11 tested STR loci of the mother’s DNA revealed alleles specific to her parents, corroborating the notion of the spontaneous character of CXCR4 mutation in the mother, which had occurred in chromosome 2 of one of the parents of the proposita.

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