Next generation sequencing identifies mutations in Colombian patients with primary immunodeficiency diseases

Background: The genetic etiology of several primary immunodeficiency diseases (PID) remains elusive. Next generation technologies represent a cost-effective and rapid first-line genetic approach for the evaluation of diseases underlying mendelian traits involved in PID which are characterized by a difficult and late diagnosis. Methods: In the PID group in Medellin (Colombia), up-today we have performed whole exome sequencing in 93 patients and relatives with severe phenotypes expecting for a gene causing disease underlying a PID. Results: From 93 WES analysis, gene causing disease have been identified in (n = 15/93) as follows: recurrent infections (n = 4/5, CYBB), BCGitis (n = 1/1, AR IL-12RB1), disseminated infection by Mycobacterium sp. (n = 1/7, AR IL-12RB1), BCGosis, salmonellosis, Mycobacterium tuberculosis and Klebsiella (n = 1, (PR)-IFNGR1), disseminated infection such as candidiasis (n = 5/5, AD- STAT1-GOF), histoplasmosis (n = 1/6, AR NCF4), invasive Corynespora cassiicola infection (n = 1/1, AR CARD9), recurrent infections and glomerulonephritis (n = 1/1, AR C3). Also, we have found several good candidate genes in a cohort of selective IgA deficiency (n = 2/23, PIK3CD, NFKB2), juvenile paracoccidioidomycosis (n = 3/3, IL17RA, IL18R1, PIK3CA) and finally, a cohort with impaired response against pneumococcal vaccines (n = 1/4, NFKBIA). We are performing further analysis in these candidate genes and exome reanalysis in the rest of patients. Conclusions: We analyzed 93 WES in patients and relatives with several PID phenotypes, we found gene causing defect (n = 15/93) from different cohort of PID patients. WES is emerging as a valuable tool to reach in a timely manner, a PID diagnosis with considerable potential to draw genotype-phenotype correlation.