Vihinen M, Belohradsky B H, Haire R N, Holinski-Feder E, Kwan S P, Lappalainen I, Lehväslaiho H, Lester T, Meindl A, Ochs H D, Ollila J, Vorechovsky I, Weiss M, Smith C I
Department of Biosciences, Division of Biochemistry, University of Helsinki, PO Box 56, Helsinki, FIN-00014, Finland.
Nucleic Acids Res. 1997 Jan 1;25(1):166-71. doi: 10.1093/nar/25.1.166.
X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations has been compiled and the recent update lists 368 entries from 318 unrelated families showing 228 unique molecular events. In addition to mutations the database lists also some polymorphisms and site-directed mutations. Each patient is given a unique patient identity number (PIN). Information is provided regarding the phenotype including symptoms. Mutations in all the five domains of BTK have been noticed to cause the disease, the most common event being missense mutations. The mutations appear almost uniformly throughout the molecule and frequently affect CpG sites forming arginine residues. These hot spots have generally pyrimidines 5'and purines 3'to the mutated cytosine. A decreased frequency of missense mutations was found in the TH, SH3 and the upper lobe of the kinase domain. The putative structural implications of all the missense mutations are given in the database showing 228 unique molecular events, including a novel missense mutation causing an R28C substitution as previously seen in the Xid mouse.
X连锁无丙种球蛋白血症（XLA）是一种由布鲁顿无丙种球蛋白血症酪氨酸激酶（BTK）编码基因突变引起的免疫缺陷病。已建立了一个BTK突变数据库（BTKbase），其最新更新列出了来自318个无关家族的368个条目，显示出228个独特的分子事件。除了突变，该数据库还列出了一些多态性和定点突变。每个患者都有一个唯一的患者识别号（PIN）。提供了有关包括症状在内的表型的信息。已注意到BTK所有五个结构域中的突变都会导致该病，最常见的事件是错义突变。这些突变几乎均匀地出现在整个分子中，并经常影响形成精氨酸残基的CpG位点。这些热点通常在突变胞嘧啶的5'端为嘧啶，3'端为嘌呤。在激酶结构域的TH、SH3和上叶中发现错义突变的频率降低。数据库中给出了所有错义突变的假定结构影响，显示出228个独特的分子事件，包括一个导致R28C替代的新型错义突变，这与之前在Xid小鼠中观察到的情况相同。
