Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome
Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome
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DOI：
10.1038/9696
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发表时间：
1999-06-01
期刊：
影响因子：
30.8
通讯作者：
Delpech, M
中科院分区：
文献类型：
--
作者：
Drenth, JPH;Cuisset, L;Delpech, M
高免疫球蛋白血症D和周期性发热综合征（HIDS; MIM 260920）是一种罕见的单基因常染色体隐性遗传疾病，其特征是反复发热，伴有淋巴结肿大、腹痛、关节受累和皮肤病变。所有患者都具有高血清IgD值（>100 U/ml），并且HIDS“发作”与强烈的急性期反应相关，其确切的病理生理学仍不清楚（2-4）。另外两种遗传性发热性疾病也有描述。家族性地中海热（MIM 249100）是一种常染色体隐性遗传疾病，主要影响地中海盆地的人群，由MEFV基因突变引起（参考文献5、6）。家族性海伯尼亚热（MIM 142680），也称为常染色体显性遗传家族性复发热，是由编码1型肿瘤坏死因子受体的基因的错义突变引起的（7-10）。在这里，我们进行全基因组搜索，以映射HIDS基因。单倍型分析：将该基因定位于12 q24的D12 S330和D12 S79之间。我们鉴定了编码甲羟戊酸激酶（MK，ATP：甲羟戊酸5-磷酸转移酶; EC 2.7.1.36）的基因MVK作为候选基因。我们表征了3个错义突变，一个92 bp的缺失源于缺失或外显子跳跃，以及一个等位基因表达的缺失。功能分析表明，在来自HIDS患者的成纤维细胞中，MK活性降低。我们的数据建立MVK作为：基因负责HIDS。
Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS; MIM 260920) is a rare, apparently monogenic, autosomal recessive disorder characterized by recurrent episodes of fever accompanied with lymphadenopathy, abdominal distress,joint involvement and skin lesions'.;All patients have high serum IgD values (>100 U/ml) and HIDS 'attacks' are associated with an intense acute phase reaction whose exact pathophysiology remains obscure(2-4). Two other hereditary febrile disorders have been described. Familial Mediterranean fever (MIM 249100) is an autosomal recessive disorder affecting mostly populations from the Mediterranean basin and is caused by mutations in the gene MEFV(refs 5,6). Familial Hibernian fever (MIM 142680), also known as autosomal: dominant familial recurrent-fever, is caused by missense mutations in the gene encoding type 1 tumour necrosis factor receptor(7-10). Here we perform a genome-wide search to map the HIDS; gene. Haplotype analysis:placed the gene at 12q24 between D12S330 and D12S79. We identified the gene MVK,: encoding mevalonate kinase (MK, ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36), as a candidate gene. We characterized 3 missense mutations, a 92-bp loss stemming from a deletion or from exon skipping, and the absence of expression of one allele Functional analysis demonstrated diminished MK activity in: fibroblasts from HIDS-patients. Our data establish MVK as the: gene responsible for HIDS.