Deep intronic mis-splicing mutation in JAK3 gene underlies T − B + NK − severe combined immunodeficiency phenotype

- Novel deep intronic mis-splicing mutation in JAK3 as a cause of T- B + NK- SCID.
- Highlighting the need for evaluation of intronic regulatory elements of known genes associated with defined phenotypes.
- For patients with a known phenotype, analysis of noncoding regions is useful before starting to search for unknown genes.

Severe combined immune deficiency (SCID) is a group of genetically heterogeneous diseases caused by an early block in T cell differentiation and present with life threatening infections, often within the first year of life. Janus kinase (JAK)3 gene mutations have been found to cause autosomal recessive T − B + SCID phenotype. In this study we describe three patients with a novel deep intronic mis-splicing mutation in JAK3 as a cause of T − B + NK − SCID highlighting the need for careful evaluation of intronic regulatory elements of known genes associated with clearly defined clinical phenotypes. We present the cases and discuss the current literature.