The Relation Between Clinical And Genic Analysis Of Agammaglobulinemia And Chronic Granulomatous Disease

Part One clinical features and pedigree analysis of BTK gene in 5 children of agammaglobulinemiaObjective: In this study, we investigated clinical features of 5 agammaglobulinemia children from 5 unrelated families of Guangxi, also analysised their Bruton's tyrosine kinase(BTK) genes and the relation between their families and BTK gene and their BTK-gene mutation type.Methods: After separating peripheral blood lymphocytes from 5 children who had been clinically suspected X-Linked agammaglobulinemia in our hospital during 2005 and 2010, we extracted their RNA to obtain cDNA by reverse transcript and their DNA, cDNA-PCR products were sequenced and the positive mutations sits also were identified by DNA sequence. We also collected relevant datas of these children to analyze the relationship between clinical phenotype and genotype.Results: Clinical results: 5 children were all boy, they all got recurrent infections, especially respiratory infections. There was no pharyngeal tonsil in 4 of 5 patients, two cases got arthritis complications; All of the cases got growth retardation and malnutrition. The level of immune globulin and CD19+ were decreased in these patients. Gene results: There were 1 non-mutation and 4 mutations, including 2 novel and 2 recurrent mutations. 2 novel mutations were both nonsense mutations, 1402 C>T(L405X)and 1344 delC(Q424X).1 mutation occurred within intronic splice-site sequence ( intron17(-2)A>T) had been reported. 1 recurrent mutation got TTTG 4 nucleotides deleted from 1713 to 1716 in RNA, that mutation made frame shift mutation. All mutation sits distributed tyrosine kinase domain.Conclusion:⑴We discovered 2 novel nonsense mutations, 4 mutations were all in tyrosine kinase domain.⑵There was some relationship between severity of clinical symptoms,complications and coding region of BTK gene mutation sites in XLA children. Part Two clinical features and pedigree analysis of CYBB gene in 2 children of CGDObjective: In this study, we investigated clinical features of 2 Chronic granulomatous disease children from 2 unrelated families of Guangxi, also analysised their CYBB genes and the relation between their families and CYBB gene and their CYBB-gene mutation type.Methods: After separating peripheral blood lymphocytes from 2 children who had been clinically suspected X-Linked Chronic granulomatous disease in our hospital during 2005 and 2009, we extracted their DNA, the positive mutations sits also were identified by sequencing 13 pairs of DNA-PCR products. We also collected relevant data of 2 children to analyze their clinical features.Results: Clinical results: 2 cases were boy, their T,B cell counts in peripheral blood were normal, serum immunoglobulin levels were risen, flow cytometry NAPDH respiratory burst oxidase activity were decreased. Generesults: There was 1 novel missense mutation which sited in NADPH domain ,1296 G>T. Another one was normal in CYBB gene.Conclusion: 1 novel missense mutation which sited in NADPH domain,1296 G>T.