'Silent' carriage of two familial Mediterranean fever gene mutations in large families with only a single identified patient
'Silent' carriage of two familial Mediterranean fever gene mutations in large families with only a single identified patient
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DOI：
10.1111/j.1399-0004.2011.01785.x
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发表时间：
2012-09-01
影响因子：
3.5
通讯作者：
Lidar, M.
中科院分区：
文献类型：
--
作者：
Camus, D.;Shinar, Y.;Lidar, M.
家族性地中海热基因中存在两种突变，没有明显的家族性地中海热（FMF），被称为表型III，由于缺乏医疗监督和秋水仙碱预防，易发生“沉默”AA淀粉样变，被称为表型II。我们试图确定表型III在只有一个受试者受FMF影响的大家庭中的患病率，以评估有转化为表型II风险的人群。这项研究共招募了7个大家庭。对兄弟姐妹进行MEFV突变筛查，并进行临床访谈以评估未被识别的FMF表现。表型III最常与V726A/E148Q基因型相关，在信息性家庭指数病例的兄弟姐妹中检测到10%，与一般人群的预期率相比增加了10倍（p < 0.01）。在指数病例为杂合子的5个家族中，有2个兄弟姐妹发现了未被注意到的“fmf样”表现，但在纯合子指数病例的兄弟姐妹中没有发现。在只有一个成员患有FMF的大家庭中，表型III的富集和隐匿性FMF的检测要求对兄弟姐妹进行常规临床评估和遗传筛查。
The presence of two mutations in the familial Mediterranean fever gene, without overt familial Mediterranean fever (FMF), designated as phenotype III, predisposes to developing 'silent' AA amyloidosis, recognized as phenotype II, due to the absence of medical supervision and colchicine prophylaxis. We sought to determine the prevalence of phenotype III in large families with only one subject affected with FMF, in order to assess the population at risk for transformation to phenotype II. A total of seven large families were recruited for the study. Siblings were screened for MEFV mutations and underwent a clinical interview to assess for unrecognized FMF manifestations. Phenotype III, most commonly associated with a V726A/E148Q genotype, was detected in 10% of siblings of index cases from informative families, corresponding to a 10-fold increase in comparison to the expected rate in the general population (p < 0.01). Unnoticed 'FMF-like' manifestations were detected among two siblings in the five families in which the index case was heterozygous, but in none of the siblings of the homozygous index cases. The enrichment for phenotype III and detection of occult FMF in large families, in which only a single member is afflicted with FMF, mandates routine clinical evaluation and genetic screening of siblings.