A novelBTKgene mutation, c.82delC (p.Arg28 Alafs^*5), in a Korean family with X-linked agammaglobulinemia

Abstract

X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton’s tyrosine kinase (BTK) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of CD19+ B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs*5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene.

Molecular alterations in the integrated diagnosis of pediatric glial and glioneuronal tumors: A single center experience

“…Controversy still arises when considering BRAF V600E as a prognostic factor for pediatric LGG. While some researchers reported it to be a useful prognostic marker for PFS and OS [15], others reported it to be a useful prognostic factor for PFS, but not OS [11]. Our results are contradicting with this latter study since we reported BRAF V600E to be associated with a worse OS but not with PFS, something that could be due to the differences in age, tumor location and extent of surgical resection between both series of patients.…”

“…Moreover, BRAF V600E mutation has been reported to abnormally up-regulate the MAPK signaling pathway [9,10]. Even though the BRAF V600E mutation responds unfavorably to conventional treatment, it represents a specific druggable target for personalized therapies with kinase inhibitors [11]. Moreover, CDKN2A has been previously shown to influence the response to treatment and outcome in BRAF V600E pediatric LGG [12][13][14].…”

Novel BTK mutation in X-linked agammaglobulinemia: Report of a 17-year-old male

“…2,12 BTK mutations are found in 80% of patients with agammaglobulinemia. 13 This gene is located on X-chromosome at Xq21.3-Xq22, consisting of 19 exons and encompasses 37.5 kilo-base (kb) pair of human genome. 13 More than thousands of different mutations have been found in BTK, with missense mutations being the most frequent ones.…”

“…13 This gene is located on X-chromosome at Xq21.3-Xq22, consisting of 19 exons and encompasses 37.5 kilo-base (kb) pair of human genome. 13 More than thousands of different mutations have been found in BTK, with missense mutations being the most frequent ones. In line with this, the mutation that we described in our patient was a novel hemizygous missense mutation (c.428A>T, p.His143Leu).…”

Pulmonary Manifestations of Predominantly Antibody Deficiencies

“…While BTK deficiency can leave the body in a state of immunodeficiency (e.g., XLA), its upregulation may lead to autoimmune states, such as rheumatoid arthritis and systemic lupus erythematosus [19], as well as malignant states, notably B-cell malignancies [23], squamous cell carcinoma, and pancreatic cancer [24]. Hundreds of variants have been identified in the gene BTK from patients with XLA [25][26][27][28][29]18] which may explain phenotypic divergence in XLA [30]. Therefore, data are integrated to investigate genotype-phenotype interactions [31].…”