Identification of a novel, CF-causing compound genotype (p.S1159P and p.Y569H) using an NGS-based assay: Novel...

A novel combination of two rare pathogenic cystic fibrosis-causing mutations, p.S1159P and p.Y569H, was detected in a patient of 17 years age who suffered from pancreatic insufficiency of unknown etiology. Both mutations were previously described in compound heterozygous patients with moderate lung disease, who carried p.F508del on the other allele. However, this newly described combination of alleles is unusually associated with general gastrointestinal manifestations. Both mutations managed to be identified by virtue of using the Ion PGM next-generation sequencing (NGS) platform, thereby making our work a “proof of concept” for clinical application of a new NGS technology in conjunction with the developed software for variant annotation.