Feghali Rudy, Ibrahim José-Noel, Salem Nabiha, Moussallem Romy, Hijazi Ghina, Attieh Charbel, Yammine Tony, Chebly Alain
Faculty of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon.
Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon.
Front Genet. 2025 Jan 17;15:1506656. doi: 10.3389/fgene.2024.1506656. eCollection 2024.
Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder, particularly present in the Mediterranean populations, and associated with pathogenic variants in the gene. This study aims to investigate the distribution of variants in a large cohort of Lebanese patients, and to explore the genotype-phenotype correlation among affected individuals. A retrospective analysis was conducted on 3,167 patients referred for sequencing at the Medical Genetics and Genomics Center(CGGM) at Saint-Joseph University of Beirut-Lebanon, from 2006 to 2023. Sanger sequencing was used to detect variants, focusing initially on hot-spot exons. Among the 3,167 patients, 46.73% (N = 1,480) carried at least one variant. The most common variants detected were M694V and V726A, both found in 28.98% of cases, followed by E148Q(27.83%) and M694I(13.98%). Moreover, Shiites and Sunni Muslims, and individuals from South and North Lebanon exhibited the highest frequency of variants. Interestingly, family history was found to be significantly higher in patients having two variants than those with one variant ( = 0.0026). The most commonly reported symptoms were fever(78%), abdominal pain(88%), joint pain(65%), and thoracic pain(46%). The genotype-phenotype correlation analysis revealed a more severe phenotype in patients carrying the M694V or V726A mutations compared to those with the homozygous E148Q genotype. This study, the largest in Lebanon, highlights the high prevalence of variants, particularly M694V and V726A, in FMF patients. Our data provide valuable insights into the genetic landscape of FMF in Lebanon and emphasize the importance of early genetic screening for a better disease management and genetic counselling.
家族性地中海热（FMF）是一种遗传性自身炎症性疾病，在地中海人群中尤为常见，与该基因的致病变异有关。本研究旨在调查一大群黎巴嫩患者中该变异的分布情况，并探讨受影响个体的基因型与表型之间的相关性。对2006年至2023年期间在黎巴嫩贝鲁特圣约瑟夫大学医学遗传学和基因组学中心（CGGM）接受该基因测序的3167例患者进行了回顾性分析。采用桑格测序法检测该基因变异，最初聚焦于热点外显子。在3167例患者中，46.73%（N = 1480）携带至少一种该基因变异。检测到的最常见变异是M694V和V726A，在28.98%的病例中均有发现，其次是E148Q（27.83%）和M694I（13.98%）。此外，什叶派和逊尼派穆斯林以及黎巴嫩南北部的个体变异频率最高。有趣的是，发现携带两种该基因变异的患者家族史显著高于携带一种变异的患者（P = 0.0026）。最常报告的症状是发热（78%）、腹痛（88%）、关节痛（65%）和胸痛（46%）。基因型与表型的相关性分析显示，与纯合E148Q基因型患者相比，携带M694V或V726A突变的患者表型更严重。这项黎巴嫩规模最大的研究突出了FMF患者中该基因变异的高患病率，尤其是M694V和V726A。我们的数据为黎巴嫩FMF的遗传格局提供了有价值的见解，并强调了早期基因筛查对于更好地进行疾病管理和遗传咨询的重要性。
