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Novel dedicator of cytokinesis 8 mutations identified by multiplex ligation‐dependent probe amplification
Author(s) -
Tóth Beáta,
Pistár Zsuzsanna,
Csorba Gabriella,
Balogh István,
Kovács Tímea,
Erdős Melinda,
Maródi László
Publication year - 2013
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12173
Subject(s) - multiplex ligation dependent probe amplification , exon , biology , genetics , mutation , microbiology and biotechnology , genomic dna , complementary dna , dna , gene
Dedicator of cytokinesis 8 (DOCK8) deficiency is an innate error of adaptive immunity characterized by recurrent infections with viruses, bacteria and fungi, very high serum IgE concentrations, and a progressive deterioration of T‐ and B‐cell‐mediated immunity. We studied the genetic and immunological features of two sisters (aged 11 and 6 yr). Mutational analysis of genomic DNA and cDNA from the patients and their parents, by a combination of PCR and bidirectional targeted sequencing, failed to localize the mutation site. However, a multiplex ligation‐dependent probe amplification (MLPA) assay revealed two novel large deletions, del1‐14 exons and del8‐18 exons, of DOCK8 in both patients. Immunoblot analysis demonstrated that DOCK8 protein was absent from the peripheral blood lymphocytes of both patients. These data suggest that compound heterozygous del1‐14 exons and del8‐18 exons mutations result in a loss of function of DOCK8 protein and a typical DOCK8 deficiency phenotype.