Two novel frame shift, recurrent and de novo mutations in the ITGB2 (CD18) gene causing leukocyte adhesion deficiency in a highly inbred North African population

We have identified four different mutations causing leukocyte adhesion deficiency (LAD) in the ITGB2 gene of patients from a highly inbred population. Two were novel single-bp deletions (1497delG and 1920delG) causing frame shift and the two others were the missense mutations G284S and R593C. In our study, the G284S was a recurrent mutation while the R593C occurred de novo. We have also characterized a novel Xba1 polymorphic site located at the 5′ end of the ITGB2 locus. Family studies showed that the 1497delG mutation segregated with this marker and the intragenic AvaII polymorphic marker, suggesting the presence of a founder effect. The observation of a heterogeneous spectrum including de novo and recurrent mutations causing LAD in a highly inbred population is rather unexpected. In view of the literature published on the molecular genetics of LAD and considering the ethnic origin of the patients studied, our findings confirm the heterogeneity of the mutations causing LAD and point out potential mutational hot spots in the ITGB2 gene

Diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: a multicenter study (vol 12, pg 1104, 2021)

Transplantation and immunomodulatio

Variability of anti-human transglutaminase testing in celiac disease across Mediterranean countries

AIM To verify the precision and accuracy of transglutaminase antibodies (TGA) assays across Mediterranean countries. METHODS This study involved 8 referral centres for celiac disease (CD) in 7 Mediterranean countries. A central laboratory prepared 8 kits of 7 blinded and randomized serum samples, with a titrated amount of Human TGA IgA. Each sample was analysed three times on three different days, with each centre running a total of 21 tests. The results were included in a blindly coded report form, which was sent to the coordinator centre. The coordinator estimated the mean coefficient of Variation (CoVar = σ/μ), the mean accuracy (Accur = Vobserved -Vreal) and the mean percent variation (Var% = [(Vobserved -Vreal)/Vreal] × 100). RESULTS The analysis showed that 79.17% of the mean variation fell between -25% and +25% of the expected value, with the accuracy and precision progressively increasing with higher titres of TGA. From values 1.25 times greater than the normal cut-off, the measurements were highly reliable. CONCLUSION TGA estimation is a crucial step for the diagnosis of CD; given its accuracy and precision, clinicians could be confident in establishing a diagnosis. © The Author(s) 2017

Diagnosis of celiac disease and applicability of ESPGHAN guidelines in Mediterranean countries: A real life prospective study

Background: We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources. Methods: A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities. Results: There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94-97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD. Conclusions: The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies. © 2017 The Author(s)