McDermott M F, Aganna E, Hitman G A, Ogunkolade B W, Booth D R, Hawkins P N
St. Bartholomew's and the Royal London School of Medicine, UK.
Arthritis Rheum. 2000 Sep;43(9):2034-40. doi: 10.1002/1529-0131(200009)43:9<2034::AID-ANR14>3.0.CO;2-J.
To investigate genetic susceptibility in the first Indian family identified as having an autosomal dominantly inherited periodic fever syndrome. The inflammatory disease was characterized chiefly by arthralgia, skin rashes, and AA amyloidosis.
Markers from known periodic fever susceptibility loci were investigated in 7 affected and 11 healthy members of a north Indian family. These included the TNFRSF1A locus (formerly known as TNFRI), which is involved in autosomal dominant tumor necrosis factor receptor-associated periodic syndrome on chromosome 12p13, the familial Mediterranean fever locus (MEFV) on chromosome 16p13, the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) locus on chromosome 12q24, and the Muckle-Wells syndrome/familial cold urticaria (MWS/FCU) locus on distal chromosome 1q44.
Linkage to both TNFRSF1A and MEFV was definitively excluded, and DNA sequencing of these genes revealed no mutations. Furthermore, there was no evidence of linkage to the HIDS locus. In contrast, significant logarithm of odds scores for 5 markers from the MWS/FCU region were obtained in this family, and the disease segregated with the same haplotype in all affected members.
We have identified an inherited inflammatory disease in a north Indian family with clinical features overlapping some of those of MWS and FCU. The susceptibility gene maps to distal chromosome 1q44, a region already implicated in both MWS and FCU. Different mutations in the same (or a closely related) gene may be responsible for an inflammatory disease with a broad phenotype among diverse ethnic populations.
对首个被鉴定为患有常染色体显性遗传周期性发热综合征的印度家庭进行遗传易感性研究。该炎症性疾病主要特征为关节痛、皮疹和AA型淀粉样变性。
对一个北印度家庭的7名患病成员和11名健康成员进行已知周期性发热易感基因座标记物的研究。这些标记物包括位于12p13染色体上与常染色体显性肿瘤坏死因子受体相关周期性综合征有关的TNFRSF1A基因座（原称为TNFRI）、位于16p13染色体上的家族性地中海热基因座（MEFV）、位于12q24染色体上的高免疫球蛋白D和周期性发热综合征（HIDS）基因座，以及位于1q44远端染色体上的穆克-韦尔斯综合征/家族性寒冷性荨麻疹（MWS/FCU）基因座。
明确排除了与TNFRSF1A和MEFV的连锁关系，对这些基因进行DNA测序未发现突变。此外，没有证据表明与HIDS基因座存在连锁关系。相反，在这个家庭中获得了来自MWS/FCU区域的5个标记物的显著优势对数分数，并且该疾病在所有患病成员中与相同的单倍型分离。
我们在一个北印度家庭中鉴定出一种遗传性炎症性疾病，其临床特征与MWS和FCU的部分特征重叠。易感基因定位于1q44远端染色体，该区域已与MWS和FCU相关。同一（或密切相关）基因中的不同突变可能导致不同种族人群中具有广泛表型的炎症性疾病。
