title: Novel dedicator of cytokinesis 8 mutations identified by multiplex ligation-dependent probe amplification.
abstract: 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.
authors.affiliation: Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Tóth
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Pistár
authors.forename: Gabriella
authors.initials: G
authors.lastname: Csorba
authors.forename: István
authors.initials: I
authors.lastname: Balogh
authors.forename: Tímea
authors.initials: T
authors.lastname: Kovács
authors.forename: Melinda
authors.initials: M
authors.lastname: Erdős
authors.forename: László
authors.initials: L
authors.lastname: Maródi
mesh_terms: D056704:Adaptive Immunity; D001483:Base Sequence; D002648:Child; D005091:Exons; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D010375:Pedigree; D017384:Sequence Deletion; D035781:Siblings
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors
keywords: dedicator of cytokinesis 8; multiplex ligation-dependent probe amplification; novel mutations