Gene And Clinical Analysis Of 5 Cases Of X-linked Agammaglobulinemia

Objective: To summarize the clinical and immunological characteristics and gene mutations of 5 children with X-linked agagoglobulemia(XLA),and to improve the understanding of XLA.Methods: Clinical information of 5 suspected cases of XLA was collected.Next generation sequencing was performed to BTK genes of the patients and their parents,and Sanger sequencing was performed to verify the mutations.Results:(1)The 5 cases are all Han nationalities,male.The age of onset was from1-month-old to 4-year-old;Intervals from disease onset to the diagnosis was made range from 8 months to 9 years;Two cases were with suspected familial history.All cases were easy to get recurrent bronchitis/pneumonia with the frequency of 3-8 episodes per year and the intervals ranging from 1 month to 3 months.2 cases were with recurrent rhinitis and sinusitis,1 case was with juvenile rheumatoid arthritis and 1 case was with thrombocytopenic purpura.(2)In physical examination,the physical developments of all cases were near normal;No superficial lymph nodes and tonsils were found;No enlargement of spleen;No abnormal of heart;lung crackles were noticed in the cases with lower respiratory tract infections.(3)No characteristic changes of CBC were noticed in all cases.The serum levels of Ig G,Ig A,Ig M were all significant lower than normal.In the subsets of peripheral lymphocytes,B lymphocytes(CD19+)were almost absent(0.02%).T lymphocytes and the subsets(CD3+,CD4+,CD8+,CD4+/CD8+),and natural killer cells(CD16+/CD56+)were near normal.(4)Gene sequencing showed hemizygous mutations of BTK inherited from their mothers in all 5 cases.Of the 5mutations,2 were splicing mutations(c.1349+5G > T,c.1632-1G > T),2 were missense mutations(c.110 T > C,c.1751 C > A),and 1 case was frameshift mutation [c.1154 del C;p.(Pro385fs)].No relationship between gene-types and clinical phenotypes was noticed.The c.1632-1G > T and c.1751 C > A mutations were newly found and had not been reported in the HGMD database.Conclusion:(1)Male patients,recurrent respiratory tract infection,absence of peripheral lymph nodes and tonsil were the main clinical manifestations of XLA.Significant decrease of all subsets of serum immunoglobulins(Ig G,Ig A,and Ig M)and the lack of B cell(CD3-CD19)are important laboratory features of XLA;(2)BTK gene sequencing was the most effective method for diagnosis.No relationship between gene-types and clinical phenotypes was noticed;(3)The c.1632-1G > T and c.1751 C > A mutations were firstly reported.