RESUMO
Context: Data on germline genetics of pituitary adenomas (PAs) using whole-exome sequencing (WES) are limited. Objective: This study investigated the germline genetic variants in patients with PAs using WES. Methods: We studied 134 consecutive functioning (80.6%) and nonfunctioning (19.4%) PAs in 61 female (45.5%) and 73 male patients (54.5%). Their median age was 34 years (range, 11-85 years) and 31 patients had microadenomas (23.0%) and 103 macroadenomas (77%). None of these patients had family history of PA or a known PA-associated syndrome. Peripheral blood DNA was isolated and whole-exome sequenced. We used American College of Medical Genetics and Genomics (ACMG) criteria and a number of in silico analysis tools to characterize genetic variant pathogenicity levels and focused on previously reported PA-associated genes. Results: We identified 35 variants of unknown significance (VUS) in 17 PA-associated genes occurring in 40 patients (29.8%). Although designated VUS by the strict ACGM criteria, they are predicted to be pathogenic by in silico analyses and their extremely low frequencies in 1000 genome, gnomAD, and the Saudi Genome Project databases. Further analysis of these variants by the Alpha Missense analysis tool yielded 8 likely pathogenic variants in 9 patients in the following genes: AIP:c.767C>T (p.S256F), CDH23:c.906G>C (p.E302D), CDH23:c.1096G>A (p.A366T), DICER1:c.620C>T (p.A207V), MLH1:c.955G>A (p.E319K), MSH2:c.148G>A (p.A50T), SDHA:c.869T>C (p.L290P) and USP48 (2 patients): c.2233G>A (p.V745M). Conclusion: This study suggests that about 6.7% of patients with apparently sporadic PAs carry likely pathogenic variants in PA-associated genes. These findings need further studies to confirm them.
RESUMO
BACKGROUND: National Registries are essential to direct current practice. Rheumatoid arthritis (RA) registries in the middle east and North Africa remain scarcely represented. OBJECTIVE: To describe a population of Saudi RA patients and to compare the findings to internationally reported data. METHODS: This is an observational study that was conducted at Doctor Soliman Fakeeh Hospital (DSFH) in Saudi Arabia. The study ran from 2014 to 2018 using a pool of 433 patients. Inclusion criteria included adults older than 18 years of age who fulfilled the 2010 American College of Rheumatology criteria for the diagnosis of RA and who were also regular visitors in our rheumatology clinics. Data were collected directly from patients and entered in a specially designed program. RESULTS: At initial presentation, 45.5% had demonstrated active disease (moderate or high disease activity) based on DAS-28-CRP scores, while 54.5% were in low disease activity or remission. The remission rates after 1 year had increased to 79.6% (345 patients), while 9.7% (42 patients) and 10.6% (46 patients) had low disease activity and moderate disease activity, respectively. It was also found that the female gender, higher Health Assessment Questionnaire-Disability Index (HAQ-DI) and longer lag1/lag2 periods were associated with higher disease activity in our population. CONCLUSION: We detected higher remission rates at 1 year of follow-up. This could be attributed to many factors, including good referral systems with easier access to biologics. We aim to expand this registry to the national level.
