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Browsing Public Health by Author "Diaeddin Sami Qamhia"

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    Investigation of the Molecular Basis of Familial Mediterranean Fever-Like Disease in Palestinian population
    (Al-Quds University, 2023-11-08) Diaeddin Sami Qamhia; ضياء الدين سامي قمحيه
    Background: Familial Mediterranean Fever (FMF), the most common inherited auto-inflammatory disease worldwide, is caused by gain-of-function mutations in the MEFV gene, which encodes the immune modulatory protein pyrin. The Familial Mediterranean Fever gene (MEFV) gene has been implicated as the main gene responsible for FMF. The aims of our study were to identify and characterize new genes involved in FMF and determine the prevalence of the known MEFV mutation associated with FMF in our patient’s cohort. Methods: clinically diagnosed FMF patients who met the Tel Hashmer’s diagnostic criteria and were confirmed to be negative for the most common mutations in exon 10 of the MEFV gene were included in our study. DNA was extracted from 22 individuals from 7 independent families and Whole Exome Sequencing (WES) was applied to 2 patients from the same family (Father and his son). Results: About 1422 patients (48.6% females and 51.4% males) with FMF were chosen to participate in our study, from 2018 till 2020, 763 patients were found to be negative for MEFV gene, and only 2 were analyzed for new genes or mutations suspecting them for FMF. Around 435 and 224 patients were found to be heterozygous and homozygous for MEFV gene mutation, respectively. Regarding the type of mutation, 595 patients were found to be likely pathogenic for MEFV gene, 222 patients were found to have variants of uncertain significance (VUS) mutation, and 605 patients were found to be pathogenic for MEFV gene mutation. The most common mutations found were R761H (41.09%), followed by V726A (18.82%), M694V (17.57%), M694I (5.7%), M680I (5.15%), A744S (3.51%), K695R (3.04%), P369S (2.73%), F479L (1.25%), and I692del (1.09%). Gender was not found to be significantly related to the presence of different mutations. Whole exome sequencing (WES), applied for 2 samples (a father and his son), showed 4 variant genes: COL3A1, ANKRD36C, WNK1, and PCDH17, that potentially may contribute to FMF-like phenotype in heterozygous variant, and MT-ND5, C1ORF109, ANKRD36B, LNP1, LRRC37A, KIR2DL4, and XKR3 in homozygous variant. Conclusion: Several candidate genes related to the FMF-like phenotype were identified in this study, and the prevalence of known MEFV mutations associated with FMF was determined.