1 - Unidade de Imunodeficiências Primárias, Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
2 - Unidade de Gastroenterologia, Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
3 - University of Cambridge, Medicine, Cambridge, United Kingdom
- 18th Biennial Meeting of The European Society for Immunodeficiencies (E-Poster)
Resumo:
Background: Very-early onset inflammatory bowel disease (VEO-IBD) is a severe, usually resistant to multiple treatments, subtype of IBD. In the last years, many rare genetic causes of VEO-IBD have been identified, allowing different therapeutic strategies. Screening of a monogenic cause was performed in every patient with infantile VEO-IBD (IBD starting before the age of two-years of age) followed in our Centre.
Methods: We performed Sanger sequencing of a specific gene in those who had distinctive features of a particular PID adding to the VEO-IBD. Whole-exome sequencing (WES) was performed in patients with isolated VEO-IBD. In these, presumably causative variants were confirmed by Sanger sequencing and functional validation was performed on the variants that were presumably causative but that had never been reported before.
Results: Thirteen patients with infantile VEO-IBD were investigated. In 4 of them, targeted-gene sequencing was diagnostic (IL10R in two patients, CYBB and G6PC3). WES was performed in the other 9 patients. We were able to identify a mutation in a gene already related with VEO-IBD in 2 of them (TTC7A and PLCG2), and in 2 patients we identified two novel variants associated with VEO-IBD (STXBP3 and ADCy7). We didn’t find a causative mutation in only 5 patients (38% of the cohort).
Conclusions: This strategy led to the diagnosis of a rare monogenic cause of VEO-IBD in 62% of the patients in this cohort, including two novel monogenic causes of VEO-IBD. This has allowed proper management and familial counselling.
Palavras Chave: VEO-IBD, WES