title: Identification of a novel, CF-causing compound genotype (p.S1159P and p.Y569H) using an NGS-based assay: Novel CF-causing compound p.S1159P and p.Y569H genotype.
abstract: 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.
authors.affiliation: Parseq Lab Co. Ltd., Saint-Petersburg, Russian Federation.
authors.forename: Tamara
authors.initials: T
authors.lastname: Simakova
authors.affiliation: Research Centre for Medical Genetics, Cystic Fibrosis Clinical Science Department, Moscow, Russian Federation.
authors.forename: Elena
authors.initials: E
authors.lastname: Kondratyeva
authors.affiliation: Russian Children's Clinical Hospital, Moscow, Russian Federation.
authors.forename: Lusine
authors.initials: L
authors.lastname: Avakian
authors.affiliation: Parseq Lab Co. Ltd., Saint-Petersburg, Russian Federation.
authors.forename: Anton
authors.initials: A
authors.lastname: Bragin
authors.affiliation: Parseq Lab Co. Ltd., Saint-Petersburg, Russian Federation.
authors.forename: Maria
authors.initials: M
authors.lastname: Zaytseva
authors.affiliation: Parseq Lab Co. Ltd., Saint-Petersburg, Russian Federation.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pavlov
mesh_terms: D000293:Adolescent; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D010188:Exocrine Pancreatic Insufficiency / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009154:Mutation; D012680:Sensitivity and Specificity
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CF mild phenotype; CF-causing genotype; Next-generation sequencing; Pancreatic insufficiency; Rare mutations