[Mutation analysis and prenatal diagnosis in families of X-linked agammaglobulinemia caused by BTK gene mutation].

Objective: To evaluate the genetic diagnostic feasibility of Bruton's tyrosine kinase (BTK) gene in three families with X-linked agammagobulinemia (XLA) birth history, mutation analysis and prenatal genetic diagnosis of BTK gene for two families with XLA.

Methods: Polymerase chain reaction (PCR) was applied to amplify the regions of exon and exon-intron boundaries of BTK gene in 3 unrelated patients of XLA and their mothers from January 2011 to June 2012. The PCR products were further analyzed by direct sequencing. Prenatal genetic diagnosis was performed by chorionic villus sampling after genotyping of mothers of probands.

Results: Three novel mutations of BTK gene were identified in 3 pedigrees of XLA. A missense mutation c.1117C > A (p.L373I) were detected in pedigree 1. The mutation was possible damage by predicting in sillico. A nonsense mutation c.126T > G (p.Y42X) was found in pedigree 2. A single base deletion mutation c.1679delC (p. P560fsX10) was found in pedigree 3. The three mutations, p.L373I, p.Y42X and p. P560fsX10 were novel. The three novel mutations were absent in the 100 normal controls. The male fetus in pedigree 3 was free of mutations identical to the proband and the female fetus in pedigree 2 was a carrier. The two families continued the pregnancies and the infants showed no symptom of XLA after one year old.

Conclusions: Three novel mutations were identified. The mutations of p.Y42X and p. P560fsX10 in BTK gene may be the major causes of pedigrees 2 and 3 with XLA. The mutation p.L373I of BTK gene is possibly the cause of pedigree 1 with XLA, but functional verification is needed. For pedigree of XLA, direct sequencing of BTK gene is available for providing genetic counseling, prenatal diagnosis.