Unusual mutations in Btk: An insertion, a duplication, an inversion, and four large deletions
Unusual mutations in Btk: An insertion, a duplication, an inversion, and four large deletions
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DOI：
10.1006/clim.1998.4629
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发表时间：
1999-01-01
影响因子：
8.6
通讯作者：
Conley, ME
中科院分区：
文献类型：
--
作者：
Rohrer, J;Minegishi, Y;Conley, ME
布鲁顿酪氨酸激酶（Btk）突变导致免疫缺陷x连锁无球蛋白血症（XLA）。在先前对101例疑似XLA患者的研究中，我们发现7例患者Btk有较大的基因组改变。最近在Btk位点上完成的100 kb连续DNA序列使我们能够详细描述这些突变并确定四种不同类型的改变。这些改变包括在内含子9 +5位置插入一个253-bp的逆转录子，在4和5外显子之间出现一个大于48 kb的反转，破坏了Btk，包括Btk外显子2到5的12.9 kb的重复，以及4个2.8到38 kb的缺失。重复和3个缺失是由于Alu重复序列的不平等交叉造成的。此外，其中三个缺失终止于Btk外显子19序列3'的一个重复序列丰富的簇内，长度为30kb，这表明该区域比Btk基因的其他区域更容易发生不平等交叉。这些研究首次报道了Btk中的插入、反转和重复，并证明了大规模测序在阐明致病突变方面的实用性。(C) 1999学术出版社。
Mutations in Bruton's tyrosine kinase (Btk) result in the immunodeficiency X-linked agammaglobulinemia (XLA). In a previous study of 101 patients with presumed XLA, we identified seven patients with large genomic alterations in Btk. The recent completion of 100 kb of contiguous DNA sequence at the Btk locus has allowed us to characterize these mutations in detail and to identify four different types of alterations. These alterations included a 253-bp retroposon insertion at position +5 within intron 9, an inversion of greater than 48 kb that disrupted Btk between exons 4 and 5, a 12.9-kb duplication including Btk exons 2 to 5, and four deletions ranging from 2.8 to 38 kb in size. The duplication and three of the deletions resulted from unequal crossovers of Alu repeats. Further, three of the deletions terminated within a repeat-rich cluster spanning 30 kb of sequence 3' of Btk exon 19, suggesting that this region was more susceptible to unequal crossovers than the rest of the Btk gene. These studies describe the first reports of an insert-ion, an inversion, and a duplication in Btk and demonstrate the utility of large-scale sequencing in the elucidation of disease-causing mutations. (C) 1999 Academic Press.