SUMMARY By running the Swedish twin registry containing about 25 000 pairs of twins of the same sex together with the central national diagnosis register of hospital inpatients, 80 twin pairs suffering from inflammatory bowel disease were found. In the ulcerative colitis group one of 16 monozygotic pairs was concordant for the disease, but all the other 20 pairs (dizygotic or unknown zygosity) were discordant. In the Crohn's disease group eight of 18 monozygotic pairs and one of 26 dizygotic pairs were concordant. The proband concordance rate among monozygotic twins was 6-3% for ulcerative colitis and 58-3% for Crohn's disease. The calculated heritability of liability based on monozygotic pairs was 0 53 and 1 0 respectively. Thus heredity as an aetiological factor is stronger in Crohn's disease than in ulcerative colitis. Monozygotic twins with Crohn's disease were more likely to be smokers than monozygotic twins with ulcerative colitis. Smoking did not explain the discordance of twin pairs with either ulcerative colitis, or Crohn's disease. The combination of identical heredity and similar smoking habit is not sufficient to cause disease.

Key Points• In MDS with ring sideroblasts, SF3B1 mutation defines a homogeneous subgroup with isolated erythroid dysplasia and favorable prognosis.• MDS with ring sideroblasts and wild-type SF3B1 is mainly characterized by multilineage dysplasia and unfavorable prognosis.Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). A high prevalence of somatic mutations of SF3B1 was reported in these conditions. To identify mutation patterns that affect disease phenotype and clinical outcome, we performed a comprehensive mutation analysis in 293 patients with myeloid neoplasm and 1% or more ring sideroblasts. SF3B1 mutations were detected in 129 of 159 cases (81%) of RARS or RCMD-RS. Among other patients with ring sideroblasts, lower prevalence of SF3B1 mutations and higher prevalence of mutations in other splicing factor genes were observed (P < .001). In multivariable analyses, patients with SF3B1 mutations showed significantly better overall survival (hazard ratio [HR], .37; P 5 .003) and lower cumulative incidence of disease progression (HR 5 0.31; P 5 .018) compared with SF3B1-unmutated cases. The independent prognostic value of SF3B1 mutation was retained in MDS without excess blasts, as well as in sideroblastic categories (RARS and RCMD-RS). Among SF3B1-mutated patients, coexisting mutations in DNA methylation genes were associated with multilineage dysplasia (P 5 .015) but had no effect on clinical outcome. TP53 mutations were frequently detected in patients without SF3B1 mutation, and were associated with poor outcome. Thus, SF3B1 mutation identifies a distinct MDS subtype that is unlikely to develop detrimental subclonal mutations and is characterized by indolent clinical course and favorable outcome. (Blood. 2015;126(2):233-241)

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Background-A familial defect in intestinal barrier function has been found in Crohn's disease. Aim-To investigate possible genetic and environmental influences on this barrier defect by studying intestinal permeability in both relatives and spouses of patients with Crohn's disease. Subjects-The study included 39 patients with Crohn's disease, 34 healthy first degree relatives, and 22 spouses. Twenty nine healthy volunteers served as controls. Methods-Intestinal permeability was assessed as the lactulose:mannitol ratio in five hour urinary excretion after oral load, both before (baseline) and after ingestion of acetylsalicylic acid. The permeability response represents the diVerence between the two tests. A ratio above the 95th percentile for controls was classified as abnormal. Results-Baseline permeability was higher in patients and spouses than in controls. An abnormal baseline permeability was seen in 36% of the patients, 23% of the spouses, 18% of the relatives, and 3% of the controls. After ingestion of acetylsalicylic acid, permeability increased significantly in all groups. Relatives were similar to patients with regard to permeability after exposure to acetylsalicylic acid, whereas spouses were similar to controls. The proportions with an abnormal permeability response to acetylsalicylic acid were 32% in patients, 14% in spouses, 41% in relatives, and 3% in controls. Conclusion-The findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn's disease. (Gut 1999;44:96-100)

The effects of smoking on the localisation and clinical course of Crohn's disease is evaluated in 231 patients. Heavy smokers (>10 cigarettes/ day) had an increased risk of operation at least once -odds ratios for heavy smokers compared with never smokers after five and 10 years were