Identification of 22 novel BTK gene variants in B cell deficiency with hypogammaglobulinemia
| Autor: | Michelle van Hee, John B. Hagan, Regan Pyle, Thomas G. Boyce, Roshini S. Abraham, Yesim Yilmaz-Demirdag, Xiangyang Dong, Sami L. Bahna, Elizabeth Varga, Tamara C. Pozos, Monica T. Kraft |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male Immunology DNA Mutational Analysis Mutation Missense Mutagenesis (molecular biology technique) X-linked agammaglobulinemia Hypogammaglobulinemia 03 medical and health sciences Young Adult 0302 clinical medicine Agammaglobulinemia hemic and lymphatic diseases medicine Agammaglobulinaemia Tyrosine Kinase Immunology and Allergy Bruton's tyrosine kinase Missense mutation Humans Site-directed mutagenesis Gene X-linked recessive inheritance Genetics B-Lymphocytes biology Infant Newborn Genetic Variation Infant Genetic Diseases X-Linked Middle Aged medicine.disease Pedigree 030104 developmental biology Phenotype Child Preschool Mutation biology.protein Female 030215 immunology |
| Zdroj: | Clinical immunology (Orlando, Fla.). 229 |
| ISSN: | 1521-7035 |
| Popis: | X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK, associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration. |
| Databáze: | OpenAIRE |
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