Ferrata Storti Foundation F anconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with FA from the Israeli inherited BMF registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 years (range: 0.1-49); 63% were offspring of consanguineous parents. One-hundred patients (90%) had at least one congenital anomaly; over 80% of the patients developed bone marrow failure; 53% underwent hematopoietic stem-cell transplantation; 33% of the patients developed cancer; no significant association was found between hematopoietic stem-cell transplant and solid tumor development. Nearly 95% of the patients tested had confirmed mutations in the Fanconi genes FANCA (67%), FANCC (13%), FANCG (14%), FANCJ (3%) and FANCD1 (2%), including twenty novel mutations. Patients with FANCA mutations developed cancer at a significantly older age compared to patients with mutations in other Fanconi genes (mean 18.5 and 5.2 years, respectively, P=0.001); however, the overall survival did not depend on the causative gene. We hereby describe a large national cohort of patients with FA, the vast majority genetically diagnosed. Our results suggest an older age for cancer development in patients with FANCA mutations and no increased incidence of solid tumors following hematopoietic stem-cell transplant. Further studies are needed to guide individual treatment and follow-up programs.

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Background: Although coeliac disease is common worldwide, little is known regarding screening patterns in unselected populations, and on real-life adherence to professional guidelines for coeliac disease diagnosis and management. Objective: To explore current practices in the diagnosis and management of coeliac disease, using data from a large Health Maintenance Organization in Israel that covers 54% of the population. Methods: A population-based electronic database of about 4.5 million individuals was reviewed during the period of 1 January 2008 to 31 December 2015. Rates and results of coeliac disease serology testing and endoscopy procedures were examined. Subgroup analysis was performed by age, sex, ethnicity and socioeconomic status. Results: Coeliac disease serology cumulative testing rate was 17.1% and 8.9% in the paediatric and adult population, respectively. The cumulative incidence of positive coeliac disease serology was 0.45% in children and 0.17% in adults, and was associated with age, sex, ethnicity and socioeconomic status sub-groups (P-value < 0.01). Gastrointestinal endoscopies were not subsequently performed in 44.1% of children and 47.1% of adults with positive coeliac disease serology. Within the study period, 36% of children and 56% of adults never achieved coeliac disease serology normalization. Conclusion: In a large real-life database, screening for coeliac disease was common. However, confirmatory intestinal biopsies were under-utilized, and coeliac disease serology often remained positive over a long period time in both children and adults.