title: A novel BTK gene mutation creates a de-novo splice site in an X-linked agammaglobulinemia patient.
abstract: Bruton's tyrosine kinase (BTK), encoded by the BTK gene, is a cytoplasmic protein critical in B cell development. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA), a primary immunodeficiency with characteristically low or absent B cells and antibodies. This report describes a five year-old boy who presented with otitis externa, arthritis, reduced immunoglobulins and no B cells. Flow cytometry showed undetectable monocyte BTK expression. Sequencing revealed a novel mutation at exon 13 of the BTK gene which created a de novo splice site with a proximal 5 nucleotide loss resulting in a truncated BTK protein. The patient still suffered from ear infection despite intravenous immunoglobulin replacement therapy. In this study, mosaicism was seen only in the mother's genomic DNA. These results suggest that a combination of flow cytometry and BTK gene analysis is important for XLA diagnosis and carrier screening.
authors: Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia. Electronic address: chearct@imr.gov.my.
authors: Chai Teng
authors: CT
authors: Chear
authors: Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Adiratna Mat
authors: AM
authors: Ripen
authors: Paediatric Department, Hospital Sultanah Aminah, Johor Bahru, Malaysia.
authors: Sharifah Adlena Syed
authors: SA
authors: Mohamed
authors: Allergy and Immunology Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors: Jasbir Singh
authors: JS
authors: Dhaliwal
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D022821:RNA Splice Sites
chemical_list: D022821:RNA Splice Sites; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human
keywords: Arthritis; BTK mutation; Splice site; X-linked agammaglobulinemia