title: A novel Bruton's tyrosine kinase gene (BTK) invariant splice site mutation in a Malaysian family with X-linked agammaglobulinemia.
abstract: X-linked agammaglobulinemia (XLA) is a rare genetic disorder caused by mutations in the Bruton's tyrosine kinase (BTK) gene. These mutations cause defects in early B cell development. A patient with no circulating B cells and low serum immunoglobulin isotypes was studied as were his mother and sister. Monocyte BTK protein expression was evaluated by flow cytometry. The mutation was determined using PCR and followed by sequencing. Flow cytometry showed the patient lacked BTK protein expression in his monocytes while the mother and sister had 62% and 40% of the monocytes showing BTK protein expressions respectively. The patient had a novel base substitution in the first nucleotide of intron 9 in the BTK gene, and the mutation was IVS9+1G<C. This mutation resulted in exon 9 skipping. This defect rendered the patient susceptible to asthma, failure to thrive, recurrent pyogenic infections, otitis media and bronchopneumonia. His mother and sister were heterozygous for this mutation. The combination of flow cytometry and genetic study is necessary in the diagnosis of X-linked agammaglobulinemia and may be used for subsequent genetic counseling, carrier detection and prenatal diagnosis.
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Chai Teng
authors.initials: CT
authors.lastname: Chear
authors.forename: Harvindar Kaur
authors.initials: HK
authors.lastname: Gill
authors.forename: Nazatul Haslina
authors.initials: NH
authors.lastname: Ramly
authors.forename: Jasbir Singh
authors.initials: JS
authors.lastname: Dhaliwal
authors.forename: Noraini
authors.initials: N
authors.lastname: Bujang
authors.forename: Adiratna Mat
authors.initials: AM
authors.lastname: Ripen
authors.forename: Saharuddin Bin
authors.initials: SB
authors.lastname: Mohamad
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D005260:Female; D005434:Flow Cytometry; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human