Moradian Mike M, Sarkisian Tamara, Amaryan Gayane, Hayrapetyan Hasmik, Yeghiazaryan Anna, Davidian Nairi, Avanesian Nare
1] Department of Medical Genetics, Morava, Glendale, California, USA [2] Department of Molecular Genetics, Center of Medical Genetics and Primary Health Care, Yerevan, Armenia.
Department of Molecular Genetics, Center of Medical Genetics and Primary Health Care, Yerevan, Armenia.
Genet Med. 2014 Mar;16(3):258-63. doi: 10.1038/gim.2013.112. Epub 2013 Aug 1.
In this study, we present clinical data from 16,000 familial Mediterranean fever patients. We also discuss the clinical manifestation of a subset of these patients and their potential symptom associations with other disorders.
Familial Mediterranean fever patients were confirmed using Tel-Hashomer criteria and were tested for the 12 most common mutations using the familial Mediterranean fever StripAssay. A total of 100 samples were selected, and their MEFV gene exons and intron junctions were completely sequenced.
We observed that in children severe phenotypes with polyserositis, erysipelas-like erythema, splenomegaly, and vasculitis are associated with high penetrance of exon 10 mutations, particularly M694V. Several forms of arthritis were associated with familial Mediterranean fever, including acute mono/oligoarthritis in the lower extremities, destructive arthritis, ankylosing spondylitis, sacroiliitis, arthritis of the hip joint, and juvenile chronic arthritis. Severe life-threatening complications, such as adhesive intestinal obstruction, renal amyloidosis, and uncommon/rare symptoms were sometimes the only form of familial Mediterranean fever manifestation.
We suggest performing familial Mediterranean fever genetic testing for patients presenting with rare/uncommon symptoms also common in other disorders, to prevent misdiagnosis or delayed diagnosis. In our experience, the most effective patient management for familial Mediterranean fever was its rapid diagnosis through genetic testing, initiation of colchicine therapy, and promotion of attack prevention through counseling.
在本研究中，我们展示了来自16000例家族性地中海热患者的临床数据。我们还讨论了这些患者亚组的临床表现及其与其他疾病潜在的症状关联。
采用泰尔-哈绍默标准确诊家族性地中海热患者，并使用家族性地中海热试纸法检测12种最常见的突变。共选取100个样本，对其MEFV基因外显子和内含子连接区进行全序列测序。
我们观察到，在儿童中，伴有多浆膜炎、丹毒样红斑、脾肿大和血管炎的严重表型与外显子10突变（尤其是M694V）的高外显率相关。几种关节炎形式与家族性地中海热相关，包括下肢急性单/寡关节炎、破坏性关节炎、强直性脊柱炎、骶髂关节炎、髋关节关节炎和青少年慢性关节炎。严重的危及生命的并发症，如粘连性肠梗阻、肾淀粉样变性以及不常见/罕见症状，有时是家族性地中海热唯一的表现形式。
我们建议对出现其他疾病中也常见的罕见/不常见症状的患者进行家族性地中海热基因检测，以防止误诊或延迟诊断。根据我们的经验，对家族性地中海热最有效的患者管理方法是通过基因检测进行快速诊断、启动秋水仙碱治疗，并通过咨询促进发作预防。
