A novel Bruton’s tyrosine kinase gene (BTK) invariant splice site mutation in a Malaysian family with X-linked agammaglobulinemia

Chear, Chai Teng; Gill, Harvindar Kaur; Ramly, Nazatul Haslina; Dhaliwal, Jasbir; Bujang, Noraini; Ripen, Adiratna Mat; Mohamad, Saharuddin Bin

doi:10.12932/ap0304.31.4.2013

Cited by 9 publications

(7 citation statements)

References 12 publications

(18 reference statements)

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“…Similar to that observed in other studies, regardless of the histological classification, we disclosed a significant association between KIAA1549-BRAF gene fusion and its anatomical location to the cerebellum for LGG [21]. While we found the fusion in 61.3% of LGG, others detected it ranging from 59.1 to 89.7% of LGG [14,15,20,22].…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2022

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Objectives: Tumors of the central nervous system (CNS) are the most common pediatric solid tumors, where low grade (LGG) and high grade gliomas (HGG) represent up to 55% of CNS tumors. Current molecular classification of these tumors results in a more accurate diagnosis and risk stratification, which ultimately enables individualized treatment strategies. Identifying known alterations is a suitable approach, particularly in developing countries, where NGS approaches are not easily accessible. We sought to assess molecular alterations in BRAF and histone 3 genes. Study design: FISH, IHC and Sanger sequencing were performed in a series of 102 pediatric glial and glioneuronal tumors. We also correlated these results with clinical and histological findings to evaluate their usefulness as diagnostic and/or prognostic tools. Results: We found that the KIAA1549-BRAF gene fusion was a relevant diagnostic tool for pilocytic astrocytoma, but not related to progression free survival (PFS) and overall survival (OS). BRAFV600E mutation was associated with a decreased OS in LGG, and with decreased PFS and OS among pilocytic astrocytomas. All HGG of the midline were H3K27M mutants, while H3G34R mutant cases were located in brain hemispheres. HGG harboring the H3K27M variant were associated with a decreased PFS and OS. Conclusions: Assessing druggable molecular markers with prognostic value is particularly important in those cases where complete resection or further radiation therapy is not possible. These potential diagnostic/prognostic markers may be suitable as further screening tests to reduce the requirement on NGS, which is not available in all laboratories. Furthermore, these results broaden data on BRAF and Histone 3 alterations in children from geographic regions, other than USA and Europe.

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Section: Discussionsupporting

confidence: 90%

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

et al. 2022

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“…Patients with XLA are particularly susceptible to respiratory infections (12,13). In our patient, Lower respiratory tract secretion specimens were obtained on bronchoscopy at the time of endotracheal intubation for respiratory failure.…”

Section: Discussionmentioning

confidence: 99%

Bruton’s agammaglobulinemia in an adult male due to a novel mutation: a case report

Liu

et al. 2016

J. Thorac. Dis.

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X-linked agammaglobulinemia (XLA) is caused by mutation in the gene coding for Bruton's tyrosine kinase (BTK), which impairs peripheral B cell maturation and hypogammaglobulinemia. In this report, we present a case of XLA in a 22-year-old adult male. Genetic testing revealed a novel mutation located at the conserved region (c.383T>C). The patient had a history of recurrent respiratory tract infection which eventually progressed to chronic type II respiratory failure. Several pathogenic bacteria were isolated on culture of respiratory secretions obtained on bronchoscopy. The patient improved on treatment with antibiotics.

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“…To date, 911 mutations in the BTK gene related to XLA have been deposited in the Human Gene Mutation Database (http:// The spectrum of these mutations includes missense mutations, nonsense mutations, splice site mutations, insertions, and deletions, with missense mutation being the most common. It has already been shown that these mutations can occur in the exons, introns, and promoters of the BTK gene [14,15]. In this study, six novel mutations were found (Table 2) The serious condition of these two patients was greatly alleviated once their diagnosis was established and IVIG treatment was initiated.…”

Section: Discussionmentioning

confidence: 60%

Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton’s tyrosine kinase (BTK) gene mutations

Gao

Duan

et al. 2020

BMC Med Genet

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Background: X-linked agammaglobulinaemia (XLA) is a rare immunodeficiency disease for which recurrent severe infection is the major clinical symptom. BTK is the main causative gene, with X chromosome recessive inheritance. However, the mutations reported to date do not fully explain the disorder. Methods: We detected the percentage of CD19+ B cells and serum immunoglobulin (IgG, IgA, and IgM) levels by flow cytometry and rate scatter immunoturbidimetry, and investigated the BTK mutation profile in 22 XLA patients using Sanger sequencing and real-time PCR. Results: We evaluated the clinical symptoms of 22 XLA patients and investigated genetic mutations present, identifying six novel mutations in the BTK gene: 2 missense mutations (c.23G > T and c.112 T > C), 2 frameshift mutations (c.522_523insC and c.1060delA), 1 large deletion (deletion of exon 2 to 5), and 1 splice-site mutation (c.1631 + 2 T > C). Prenatal diagnoses were performed in six families (F10, F11, F15, F18, F20 and F21), with the following results: the male fetus in Family 10 (F10) did not carry the c.922_923delGA mutation; the male fetus in Family 15 (F15) did not carry the c.1631 + 1G > T splicing mutation; the female fetus in Family 20 (F20) did not carry the c.1931 T > C mutation; the female fetus in Family 21 (F21) did not carry the large deletion mutation. Hence, these four fetuses are not likely to develop XLA. Male fetuses with c.1060delA and c.1684C > T mutations were identified in Family 11 and Family 18, respectively. The pregnant woman in F18 chose to terminate the pregnancy, whereas the pregnant woman in F11 chose to continue the pregnancy. Conclusion: We confirmed the diagnosis of 22 XLA patients from 22 unrelated families and detected six new pathogenic mutations. Prenatal diagnosis was performed in six families. Early genetic diagnosis and routine lifelong immunoglobulin replacement therapy can prevent and treat infections in XLA children, saving their lives.

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A novel Bruton’s tyrosine kinase gene (BTK) invariant splice site mutation in a Malaysian family with X-linked agammaglobulinemia

Cited by 9 publications

References 12 publications

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

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

Bruton’s agammaglobulinemia in an adult male due to a novel mutation: a case report

Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton’s tyrosine kinase (BTK) gene mutations

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