Clinical and mutational characteristics of X-linked agammaglobulinemia and its carrier identified by flow cytometric assessment combined with genetic analysis

Kanegane, Hirokazu; Futatani, Takeshi; Wang, Yue; Nomura, Keiko; Shinozaki, Kazumi; Matsukura, H; Kubota, Takeo; Tsukada, Satoshi; Miyawaki, Toshio

doi:10.1067/mai.2001.120133

Cited by 88 publications

(58 citation statements)

References 29 publications

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“…All of them but two (patients' 12 and 13 mothers) presented the mutation previously found in their sons (Table 1), although only 8 had an affected male family member other than their son. So, the mutated allele was present in somatic cells from 22 of 24 mothers of males with sporadic disease and proven mutations in BTK, similarly as seen in previous reports (Futatani et al, 1998;Conley et al, 1998;García Rodríguez et al, 2001;Kanegane et al, 2001).…”

Section: Resultssupporting

confidence: 85%

“…However, these patients may have mutations in BTK that are difficult to identify (Gaspar et al, 1998;Futatani et al, 1998) or they may have defects (i.e., in genes encoding Ig heavy chain constant mu, lambda 14.1, CD79a, B cell linker protein) that are phenotypically similar to XLA but genotypically different (Conley et al, 1998;Kanegane et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

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Bruton tyrosine kinase gene mutations in Argentina

et al. 2003

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The block in differentiation from pro-B to pre-B cells results in a selective defect in the humoral immune response characteristic of human X-linked agammaglobulinemia (XLA). Mutations of Bruton tyrosine kinase (BTK) gene have been identified as the cause of XLA. Mutation detection is the most reliable method for making a definitive diagnosis, except when clinical and laboratory findings are distinctive and coupled with history of X-linked inheritance. To provide a definitive diagnosis to 40 families incorporated in the Argentinian Primary Immunodeficiencies Registry we analysed the BTK gene by SSCP analysis as screening method for XLA, followed by direct sequencing. The molecular defect was localized in 45 patients from 34 unrelated families. From the 34 independent mutations identified, 16 were previously undescribed, 31 were unique mutations, 22 were exonic single nucleotide changes (16 missense and 6 nonsense) and four intronic mutations. Because five families had clinical, immunological and inheritance data sufficient for a definitive diagnosis, our study allowed 37 patients from 29 families previously categorized probable/ possible XLA, have now definitive diagnosis leading to appropriate genetic counseling.

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Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Bruton tyrosine kinase gene mutations in Argentina

et al. 2003

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“…BTK mutation analysis was performed by direct sequencing of complementary DNA and all 19 exons and exon-intron boundaries using genomic DNA as described previously. 11,12 Fluorescence in situ hybridization Peripheral blood mononuclear cells from patients and controls were stimulated in culture with phytohemagglutinin for 72 h, followed by treatment with a 0.075 M. KCl solution and fixation with Carnoy's solution (3:1 methanol and acetic acid) for metaphase preparation. A BTK-TIMM8A-specific genomic probe (5231 bp long) was prepared using the LA-PCR Kit (Takara, Kyoto, Japan) with primer pairs reflecting exon 19 of BTK and exon 2 of TIMM8A (5¢-AGCATTCTGGCATGAATGTTCCCTGAAC-3¢ and 5¢-ATCTCTCCGGGT TGCAGATAATAACTG C-3¢, respectively).…”

Section: Gene Analysis Of Btkmentioning

confidence: 99%

Genetic analysis of contiguous X-chromosome deletion syndrome encompassing the BTK and TIMM8A genes

et al. 2011

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Patients with X-linked agammaglobulinemia (XLA) can present with sensorineural deafness. This can result from a gross deletion that not only involved the Bruton's tyrosine kinase (BTK) gene, but also TIMM8A, mutations in which underlie the MohrTranebjaerg syndrome (MTS). We analyzed the genomic break points observed in three XLA-MTS patients and compared these with deletions break points from XLA patients. Patient 1 had a 63-kb deletion with break points in intron 15 of BTK and 4 kb upstream of TAF7L. Patients 2 and 3 had 149.7 and 196 kb deletions comprising BTK, TIMM8A, TAF7L and DRP2. The break points in patients 1 and 3 were located in Alu and endogenous retrovirus (ERV) repeats, whereas the break points in patient 2 did not show involvement of transposable elements. Comparison of gross deletion sizes and involvement of transposable elements in XLA and XLA-MTS patients from the literature showed preferential involvement of Alu elements in smaller deletions (o10 kb). These results show further insights into the molecular mechanisms underlying gross deletions in patients with primary immunodeficiency.

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“…Using intracellular staining of BTK on monocytes, Kanegane et al (2001) demonstrated a 98% detection rate of BTK deficiency. In this method, PBMC's were separated by Ficoll-Hypaque gradient centrifugation, stained with phycoerythrin-labeled anti-CD14 and anti-BTK mAbs followed by an IgG1 control and additional incubation with FITC-conjugated goat antimouse IgG1 antibody for FACS analysis (Kanegane et al, 2001). This assay should be used in conjunction with DNA sequencing for a definitive diagnosis.…”

Section: Flow Cytometric Assays For Diagnosismentioning

confidence: 99%