Drenth J P, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser S D, de Jong J G, Beckmann J S, van der Meer J W, Delpech M
Laboratoire de Génétique Moléculaire Humaine, Institut Cochin de Génétique Moléculaire and Hôpital Cochin, Assistance Publique-Hopitaux de Paris, France.
Nat Genet. 1999 Jun;22(2):178-81. doi: 10.1038/9696.
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. 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 I tumour necrosis factor receptor. 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.
高免疫球蛋白D血症和周期性发热综合征（HIDS；MIM 260920）是一种罕见的、明显单基因的常染色体隐性疾病，其特征为发热反复发作，并伴有淋巴结病、腹部不适、关节受累和皮肤损害。所有患者血清IgD值均高（>100 U/ml），且HIDS“发作”与强烈的急性期反应相关，其确切病理生理学仍不清楚。另外还描述了两种遗传性发热疾病。家族性地中海热（MIM 249100）是一种常染色体隐性疾病，主要影响地中海盆地人群，由MEFV基因突变引起（参考文献5,6）。家族性爱尔兰热（MIM 142680），也称为常染色体显性家族性复发性发热，由编码I型肿瘤坏死因子受体的基因突变引起。我们进行了全基因组搜索以定位HIDS基因。单倍型分析将该基因定位于12q24上D12S330和D12S79之间。我们鉴定出编码甲羟戊酸激酶（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。我们鉴定了3个错义突变、一个由缺失或外显子跳跃导致的92bp缺失以及一个等位基因的表达缺失。功能分析表明HIDS患者成纤维细胞中的MK活性降低。我们的数据证实MVK是导致HIDS的基因。
