背景:家族性地中海热(FMF)是最常见的单基因自身炎性疾病,由隐性遗传MEFV基因突变引起。最常见的MEFV突变在外显率和疾病严重程度上有所不同。我们调查了三种最常见的MEFV基因突变的基因型-表型关联(M680I,M694V,和V726A)在埃及FMF儿童中,关于临床特征,严重程度,和秋水仙碱反应。
方法:我们对2010年至2015年来自开罗大都会的500名FMF儿科患者的医疗登记进行了回顾性分析。诊断基于Tel-Hashomer临床诊断标准。收集临床数据和基线调查。通过扩增-难治性突变系统(ARMS)-PCR方法进行突变分析。
结果:男性占54%,年龄2至18岁。最常见的症状是腹痛,发烧,和关节痛.临床特征主要与M694V突变相关,无论是纯合还是杂合,双,或者三倍。在患者中,94.6%对秋水仙碱有完全反应。在受益于秋水仙碱的患者中,42.5%有M694V/V726A,21.6%有M694V/V726A/M680I,21.1%为M694V基因型。简单杂合M694V或V726A突变在57.1%和50%的病例中表现出中等表型,分别。在21.7%和65.2%的病例中,纯合M694V突变表现为中度和重度表型。分别。在48.3%和33.8%的病例中,与中度或重度疾病相关的化合物M694V/V726A突变,分别。
结论:本研究涵盖了迄今为止最大的埃及儿科FMF组,以探索其基因型-表型关联。我们的结果支持这样的观点,即基因型影响临床表现的表型,疾病严重程度,和秋水仙碱反应。
结论:•本研究涵盖了迄今为止最大的受FMF影响的埃及儿科患者群体,以探索他们的基因型-表型关联。•我们的结果支持这样的观点,即基因型影响临床表现的表型,疾病的严重程度,以及对秋水仙碱治疗的反应。
BACKGROUND: Familial Mediterranean fever (FMF) is the most prevalent monogenic autoinflammatory disease, caused by recessively inherited MEFV gene mutations. The most frequent MEFV mutations differ in penetrance and disease severity. We investigated the genotype-phenotype associations of the three most frequent MEFV gene mutations (M680I, M694V, and V726A) in Egyptian FMF children, regarding clinical features, severity, and colchicine response.
METHODS: We conducted a retrospective analysis of the medical registries of 500 FMF pediatric patients from Metropolitan Cairo between 2010 and 2015. The diagnosis was based on the Tel-Hashomer clinical diagnostic criteria. Clinical data and baseline investigations were collected. Mutation analysis was performed by the amplification-refractory mutation system (ARMS)-PCR method.
RESULTS: Males represented 54% and ages ranged from 2 to 18 years. The most frequent symptoms were abdominal pain, fever, and arthralgia. Clinical features mostly associated with M694V mutation either homozygous or heterozygous whether simple, double, or triple. Of the patients, 94.6% completely responded to colchicine. Among patients benefiting from colchicine, 42.5% had M694V/V726A, 21.6% had M694V/V726A/M680I, and 21.1% had M694V genotype. Simple heterozygous M694V or V726A mutations conveyed a moderate phenotype in 57.1% and 50% of cases, respectively. Homozygous M694V mutation showed moderate and severe phenotypes in 21.7% and 65.2% of cases, respectively. Compound M694V/V726A mutation associated with moderate or severe disease in 48.3% and 33.8% of cases, respectively.
CONCLUSIONS: This
study encompasses the largest group of Egyptian pediatric FMF up to date to explore their genotype-phenotype associations. Our results support the notion that the genotype influences the phenotype as regards clinical manifestations, disease severity, and colchicine response.
CONCLUSIONS: • This
study encompasses the largest group of Egyptian pediatric patients affected by FMF up to date to explore their genotype-phenotype associations. • Our results support the notion that the genotype influences the phenotype as regards the clinical manifestations, the disease severity, and the response to colchicine treatment.