UO Pediatria II Reumatologia, Istituto G Gaslini, Genova, Italy.
Ann Rheum Dis. 2012 Dec;71(12):1961-5. doi: 10.1136/annrheumdis-2011-200977. Epub 2012 May 12.
To evaluate the actual impact of MEFV mutations on clinical manifestations associated with fever attacks in Caucasian children with periodic fever.
113 children carrying MEFV mutations (44 with mutations in two alleles, 69 heterozygous) and 205 children negative for mutations in genes associated with periodic fevers were analysed. The following groups of patients were considered: patients carrying two high penetrance mutations (M694V, M694I, M680I); one high, one low penetrance mutation; two low penetrance mutations; one high penetrance mutation; one low penetrance mutation; genetically negative patients.
Patients with two MEFV mutations displayed a shorter duration of fever attacks and higher prevalence of a positive family history than patients carrying one MEFV mutation and genetically negative patients. Severe abdominal pain, chest pain and pleurisy were also more frequent in patients with two MEFV mutations compared with children with one MEFV mutation and genetically negative patients. Conversely, a higher frequency of exudative and erythematous pharyngitis, enlargement of cervical lymph nodes, aphthous stomatitis and non-specific skin rash was observed in genetically negative patients and, to a lesser extent, in patients with one MEFV mutation. The frequency of 'familial Mediterranean fever (FMF)-like symptoms' decreases from patients carrying two high penetrance mutations towards patients with a single low penetrance mutation with an opposite trend for 'periodic fever, aphthous stomatitis, pharyngitis, adenitis-like symptoms'.
This clinical observation supports recent findings contrasting the notion of FMF being a pure autosomal recessive disorder associated with recurrence of mutations leading to loss of protein function. A dosage effect could be invoked, giving rise to symptom onset even in the presence of one wild-type allele.
评估 MEFV 突变对伴有发热发作的白种人周期性发热儿童相关临床表现的实际影响。
分析了 113 名携带 MEFV 突变的儿童（44 名突变存在于两个等位基因，69 名杂合子）和 205 名未携带与周期性发热相关基因的突变的儿童。考虑了以下几组患者：携带两个高外显率突变（M694V、M694I、M680I）的患者；一个高外显率、一个低外显率突变的患者；两个低外显率突变的患者；一个高外显率突变的患者；一个低外显率突变的患者；基因阴性的患者。
与携带一个 MEFV 突变和基因阴性的患者相比，携带两个 MEFV 突变的患者发热发作时间更短，阳性家族史的发生率更高。严重腹痛、胸痛和胸膜炎在携带两个 MEFV 突变的患者中也比携带一个 MEFV 突变和基因阴性的患者更常见。相反，基因阴性的患者和携带一个 MEFV 突变的患者中渗出性和红斑性咽炎、颈淋巴结肿大、阿弗他口炎和非特异性皮疹的发生率更高，而携带一个 MEFV 突变的患者的发生率较低。从携带两个高外显率突变的患者到携带单个低外显率突变的患者，“家族性地中海热（FMF）样症状”的频率降低，而“周期性发热、阿弗他口炎、咽炎、淋巴结炎样症状”的频率则呈相反趋势。
这些临床观察结果支持了最近的发现，即 FMF 不仅仅是一种与突变重复导致蛋白功能丧失相关的纯常染色体隐性遗传疾病。可以引入剂量效应，即使存在一个野生型等位基因，也会导致症状发作。
