Mutations in Btk in patients with presumed X-linked agammaglobulinemia
Mutations in Btk in patients with presumed X-linked agammaglobulinemia
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DOI：
10.1086/301828
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发表时间：
1998-05-01
影响因子：
9.8
通讯作者：
Rohrer, J
中科院分区：
文献类型：
--
作者：
Conley, ME;Mathias, D;Rohrer, J
1993年，两组研究人员发现，x连锁无球蛋白血症（XLA）是由酪氨酸激酶（现在称为Btk）的突变引起的。大多数实验室已经能够在假定患有XLA的80%-90%的男性中检测到Btk突变。其余患者可能具有难以识别的Btk突变，或者他们可能具有与XLA表型相似但基因型不同的缺陷。我们分析了101个被诊断患有XLA的男性家庭。在有一人以上受影响家庭成员的40个家庭中，有38个家庭发现了Btk突变，在有散发疾病的61个家庭中有56个家庭发现了Btk突变。排除免疫荧光研究无法证实XLA特征的B细胞数量显著减少的患者，46例推测为散发性XLA的患者中有43例发现Btk突变。根据广泛的Btk分析结果，其余三名患者中有两名存在正常B细胞发育所需的其他基因缺陷，第三名患者不太可能患有XLA。我们的技术无法在一名有家族病史和实验室结果提示XLA的男性中发现Btk突变。49名患有散发疾病并已证实存在Btk突变的男性的母亲中，有41名母亲的DNA样本与她们儿子身上发现的突变呈阳性。在其他8个家族中，突变出现在母种系中。在20个家庭中，单倍型分析表明新突变起源于外祖父或曾祖父。这些研究表明，90%-95%推定患有XLA的男性有Btk突变。其他病人可能在其他基因上有缺陷。
In 1993, two groups showed that X-linked agammaglobulinemia (XLA) was due to mutations in a tyrosine kinase now called Btk. Most laboratories have been able to detect mutations in Btk in 80%-90% of males with presumed XLA. The remaining patients may have mutations in Btk that are difficult to identify, or they may have defects that are phenotypically similar to XLA but genotypically different. We analyzed 101 families in which affected males were diagnosed as having XLA. Mutations in Btk were identified in 38 of 40 families with more than one affected family member and in 56 of 61 families with sporadic disease. Excluding the patients in whom the marked decrease in B cell numbers characteristic of XLA could not be confirmed by immunofluorescence studies, mutations in Btk were identified in 43 of 46 patients with presumed sporadic XLA. Two of the three remaining patients had defects in other genes required for normal B cell development, and the third patient was unlikely to have XLA, on the basis of results of extensive Btk analysis. Our techniques were unable to identify a mutation in Btk in one male with both a family history and laboratory findings suggestive of XLA. DNA samples from 41 of 49 of the mothers of males with sporadic disease and proven mutations in Btk were positive for the mutation found in their son. In the other 8 families, the mutation appeared to arise in the maternal germ line. In 20 families, haplotype analysis showed that the new mutation originated in the maternal grandfather or great-grandfather. These studies indicate that 90%-95% of males with presumed XLA have mutations in Btk. The other patients are likely to have defects in other genes.