Diagnostic yield of repeat genetic testing in idiopathic chronic pancreatitis.

Genetic testing is performed for unexplained pancreatitis. The aim of this study was to evaluate the diagnostic value of repeating genetic testing in idiopathic pancreatitis when new predisposing genes are identified. We investigated 330 patients who were initially screened for PRSS1, SPINK1 and CFTR genes. A new analysis was performed by Next-Generation Sequencing (NGS) for PRSS1, SPINK1, CFTR, CTRC, CASR, CPA1, TRPV6 genes and the CEL-HYB1 allele in clinical practice, and patients were included in our cohort study. Additional rare variants were identified in 7.3 % of the patients. Screening for new pancreatitis genes is recommended when initial screening is limited. Routine use of NGS is a useful diagnostic tool in these cases.

Familial Mediterranean fever among patients from Karabakh and the diagnostic value of MEFV gene analysis in all classically affected populations.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal-recessive disorder that is common in Armenian, Turkish, Arab, and Sephardic Jewish populations. Its clinical diagnosis is one of exclusion, with the patients displaying nonspecific symptoms related to serosal inflammation. MEFV gene analysis has provided the first objective diagnostic criterion for FMF. However, in the absence of an identified mutation (NI/NI genotype), both the sensitivity of the molecular analyses and the involvement of the MEFV gene in FMF are called into question. The present study was designed to further evaluate the diagnostic value of MEFV analysis in another population of Mediterranean extraction. METHODS: The MEFV gene was screened for mutations in 50 patients living in Karabakh (near Armenia) who fulfilled the established criteria for FMF. In addition, we analyzed published series of patients from the above-mentioned at-risk populations. RESULTS: The mutation spectrum in Karabakhian patients, which consisted of only 6 mutations (with 26% of NI alleles), differed from that reported in Armenian patients. Strikingly, among patients from Karabakh and among all classically affected populations, the distribution of genotypes differed dramatically from Hardy-Weinberg equilibrium (P = 0.0016 and P < 0.00001, respectively). These results, combined with other population genetics-based data, revealed the existence of an FMF-like condition that, depending on the patients' ancestry, was shown to affect 85-99% of those with the NI/NI genotype. CONCLUSION: These data illuminate the meaning of negative results of MEFV analyses and show that in all populations evaluated, most patients with the NI/NI genotype had disease that mimicked FMF and was unrelated to the MEFV gene. Our findings also demonstrate the high sensitivity of a search for very few mutations in order to perform a molecular diagnosis of MEFV-related FMF.