biostudies-literatureUnknown59(10)Bertoli-Avella A<h4>Purpose</h4>We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause.<h4>Methods</h4>Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed.<h4>Results</h4>We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in <i>AGR2</i>, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant <i>AGR2</i> Journal of medical genetics993-1001https://www.ebi.ac.uk/biostudies/studies/S-EPMC9554030biostudies-literatureA disorder clinically resembling cystic fibrosis caused by biallelic variants in the <i>AGR2</i> gene.PMC9554030Al Menabawy NJamhawi AUrzi AMoteleb Selim LAAlharbi NSAlghamdi MATripolszki KHajjari ZAloraimi SPaknia OAl Shidhani KBauer PAl Shehhi MGilani NAlfadhel MArabi HVenselaar HSaeed AAbdelrahman MKarageorgou VDemuth LPareira CMorales-Torres GChalabi DNRadefeldt MAljaedi HMarais AHotakainen RAl-Ali RCozma CAmeziane NCheema HAnjum NAl-Muhsen SBertoli-Avella ABusehail MAlShaikh MFisher SKhan SfalseA disorder clinically resembling cystic fibrosis caused by biallelic variants in the <i>AGR2</i> gene.<h4>Purpose</h4>We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause.<h4>Methods</h4>Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed.<h4>Results</h4>We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in <i>AGR2</i>, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant <i>AGR2</i> 2022-01-01T00:00:00Z2022 Oct2026-06-12T09:49:45.903Z2024-11-11T23:27:56.206ZS-EPMC95540303495283210.1136/jmedgenet-2021-108150