A novel non-frameshift ADA deletion detected by whole exome sequencing in an Iranian family with severe combined immunodeficiency

Abstract

Severe combined immunodeficiency (SCID) comprises a heterogeneous group of genetic disorders caused by early defects in the development and function of T cells. Other lymphocyte lineages (B and/or natural killer cells) are variably affected. With a worldwide frequency of approximately 1:50,000 live births, SCID may result from diverse mutations in over 16 genes. Whole-exome sequencing (WES) provides an opportunity for parallel screening of all those genes. This approach is also useful for genetic diagnosis in parents whose infant expired before genetic testing. Here, we describe a heterozygous novel non-frameshift deletion (c.587_598del p.196_199del) in the adenosine deaminase (ADA) gene identified by WES in healthy parents of an expired child with SCID. The mutation was subsequently confirmed to be homozygous in the deceased baby whose left-over blood sample volume was insufficient for direct WES analysis. In conclusion, we here describe a novel mutation in ADA, a well-known SCID gene.