Incidence of Shwachman-Diamond syndrome

No abstract availabl

Absence of acquired copy number neutral loss of heterozygosity (CN-LOH) of chromosome 7 in a series of 10 patients with Shwachman-Diamond syndrome

We report that acquired copy number neutral loss of heterozygosity (CN-LOH) of chromosome 7 was not identified in a series of 10 patients with Shwachman\u2013Diamond syndrome (SDS)

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs

IGARIS (Iatrogenic Ghost Allergy and Reflux Syndrome)

5nononemixedTornese G, Cannioto Z, Marchetti F, Martelossi S, Ventura A.Tornese, G; Cannioto, Z; Marchetti, F; Martelossi, S; Ventura, A

IBD and IBD mimicking enterocolitis in children younger than 2 years of age

Inflammatory bowel disease (IBD) is uncommon in children younger than 2 years of age. The criteria for differentiating IBD from other diseases with similar clinical presentation is unclear. We describe 16 patients who, between 1984 and 2004, received a histological diagnosis of IBD during the first two years of life. Six patients presented with histological Crohn's disease, eight with ulcerative colitis and two with indeterminate colitis. The median age at diagnosis was 125 days (range 1 day to 18 months) and the medium follow up was 89 months (range 65 days to 20 years). The disease appeared to be very severe: four children (25%) underwent total parenteral nutrition (TPN), two received colectomy (12.5%) and three patients died. Many of the patients required an aggressive, multidrug, immunosuppressive approach (azathioprine [AZA], Infliximab, thalidomide, cyclosporine A). One child presented with a hypogammaglobulinaemia without any specific immunodeficiency, while in the other patients, Wiskott-Aldrich syndrome (WAS) (4 cases) and chronic granulomatous disease (CGD) (2 cases) were identified. In 6/16 cases, allergic colitis was first considered; these cases initially underwent cow's milk protein-free diet as the only therapy before IBD was finally diagnosed. In conclusion, early IBD has a severe prognosis and often needs an aggressive therapeutic approach. Furthermore, an improper diagnosis of allergic colitis might cause an important diagnostic delay. Some severe immunodeficiencies, such as WAS and CGD, may represent a problem in terms of differential diagnosis and might be wrongly diagnosed as very early onset IBD