Open AccessCase Report: Whole exome sequencing identifies a novel frameshift insertion c.1325dupT (p.F442fsX2) in the tyrosine kinase domain of BTK gene in a young Indian individual with X-linked agammaglobulinemia
Author(s) -
Amit Rawat,
Shamsudheen Vellarikkal,
Ankit Verma,
Rijith Jayarajan,
Anju Gupta,
Surjit Singh,
Anita Chopra,
Rajive Kumar,
Vinod Scaria,
Sridhar Sivasubbu
Publication year - 2016
Publication title -
f1000research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.099
H-Index - 60
ISSN - 2046-1402
DOI - 10.12688/f1000research.9472.1
Subject(s) - exome sequencing , x linked agammaglobulinemia , frameshift mutation , sanger sequencing , bruton's tyrosine kinase , exome , genetics , primary immunodeficiency , medicine , immunophenotyping , biology , tyrosine kinase , gene , mutation , immune system , signal transduction , flow cytometry
X-linked agammaglobulinemia (XLA) is an extremely rare inherited primary immunodeficiency characterized by recurrent bacterial infections, decrease in number of mature B cells and low serum immunoglobulins. XLA is caused by mutations in the gene encoding Bruton's tyrosine kinase. We report a case of a young Indian boy suspected to have XLA. Immunophenotyping was performed for the affected child using CD20, CD19 and CD3 antibodies. Whole exome sequencing was performed using trio-based approach. The variants were further analyzed using capillary sequencing in the trio as well as maternal grandmother. Initial immunophenotyping in the affected child showed decreased count of CD19+ B cells. To strengthen the clinical findings and confirm the diagnosis of XLA, we performed whole exome sequencing. Our analysis identified a novel frameshift insertion (c.1325dupT) in the BTK gene, which was further validated by Sanger sequencing. Our approach shows the potential in using whole exome sequencing to pinpoint the molecular lesion, enabling timely diagnosis and genetic counseling, and potentially offering prenatal genetic testing for the family.