BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis. METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected. RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT. CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.
BACKGROUND AND AIMS: Multiple monogenic disorders present as very early onset inflammatory bowel disease (VEO-IBD) or as IBD with severe and atypical features. Establishing a genetic diagnosis may change patients' management and prognosis. In this study, we describe the diagnostic approach to suspected monogenic IBD in a real clinical setting, discussing genetic and phenotypic findings and therapeutic implications of molecular diagnosis. METHODS: Information of patients with VEO-IBD and early onset IBD with severe/atypical phenotypes (EO-IBD s/a) managed between 2008-2017 who underwent a genetic workup were collected. RESULTS: Ninety-three patients were included, and 12 (13%) reached a genetic diagnosis. Candidate sequencing (CS) was performed in 47 patients (50%), and next generation sequencing (NGS) was performed in 84 patients (90%). Candidate sequencing had a good diagnostic performance only when guided by clinical features specific for known monogenic diseases, whereas NGS helped finding new causative genetic variants and would have anticipated one monogenic diagnosis (XIAP) and consequent bone marrow transplant (BMT). Patients with monogenic IBD more frequently were male (92% vs 54%; P = 0.02), had extraintestinal findings (100% vs 34%; P < 0.001), and had disease onset ≤1 month of life (25% vs 1%; P = 0.006). Genetic diagnosis impacted patient management in 11 patients (92%), 7 of whom underwent BMT. CONCLUSION: A genetic diagnosis can be established in a significant proportion of suspected monogenic IBD and has an impact on patients' management. Candidate sequencing may be deployed when clinical findings orientate toward a specific diagnosis. Next generation sequencing should be preferred in patients with nonspecific phenotypes.
Authors: Lauren V Collen; David Y Kim; Michael Field; Ibeawuchi Okoroafor; Gwen Saccocia; Sydney Driscoll Whitcomb; Julia Green; Michelle Dao Dong; Jared Barends; Bridget Carey; Madison E Weatherly; Shira Rockowitz; Piotr Sliz; Enju Liu; Alal Eran; Leslie Grushkin-Lerner; Athos Bousvaros; Aleixo M Muise; Christoph Klein; Vanessa Mitsialis; Jodie Ouahed; Scott B Snapper Journal: J Crohns Colitis Date: 2022-09-08 Impact factor: 10.020
Authors: Eileen Crowley; Neil Warner; Jie Pan; Sam Khalouei; Abdul Elkadri; Karoline Fiedler; Justin Foong; Andrei L Turinsky; Dana Bronte-Tinkew; Shiqi Zhang; Jamie Hu; David Tian; Dalin Li; Julie Horowitz; Iram Siddiqui; Julia Upton; Chaim M Roifman; Peter C Church; Donna A Wall; Arun K Ramani; Daniel Kotlarz; Christoph Klein; Holm Uhlig; Scott B Snapper; Claudia Gonzaga-Jauregui; Andrew D Paterson; Dermot P B McGovern; Michael Brudno; Thomas D Walters; Anne M Griffiths; Aleixo M Muise Journal: Gastroenterology Date: 2020-02-19 Impact factor: 22.682
Authors: Holm H Uhlig; Fabienne Charbit-Henrion; Daniel Kotlarz; Dror S Shouval; Tobias Schwerd; Caterina Strisciuglio; Lissy de Ridder; Johan van Limbergen; Marina Macchi; Scott B Snapper; Frank M Ruemmele; David C Wilson; Simon P L Travis; Anne M Griffiths; Dan Turner; Christoph Klein; Aleixo M Muise; Richard K Russell Journal: J Pediatr Gastroenterol Nutr Date: 2021-03-01 Impact factor: 3.288
Authors: Valentina Boz; Erica Valencic; Martina Girardelli; Alessia Pin; Laura Gàmez-Diaz; Alberto Tommasini; Sara Lega; Matteo Bramuzzo Journal: Front Immunol Date: 2021-02-26 Impact factor: 7.561