Division of Clinical Research, Saitama Children's Medical Center, Saitama, Japan.
J Hum Genet. 2011 Aug;56(8):577-82. doi: 10.1038/jhg.2011.61. Epub 2011 Jul 14.
Patients with X-linked agammaglobulinemia (XLA) can present with sensorineural deafness. This can result from a gross deletion that not only involved the Bruton's tyrosine kinase (BTK) gene, but also TIMM8A, mutations in which underlie the Mohr-Tranebjærg syndrome (MTS). We analyzed the genomic break points observed in three XLA-MTS patients and compared these with deletions break points from XLA patients. Patient 1 had a 63-kb deletion with break points in intron 15 of BTK and 4 kb upstream of TAF7L. Patients 2 and 3 had 149.7 and 196 kb deletions comprising BTK, TIMM8A, TAF7L and DRP2. The break points in patients 1 and 3 were located in Alu and endogenous retrovirus (ERV) repeats, whereas the break points in patient 2 did not show involvement of transposable elements. Comparison of gross deletion sizes and involvement of transposable elements in XLA and XLA-MTS patients from the literature showed preferential involvement of Alu elements in smaller deletions (<10 kb). These results show further insights into the molecular mechanisms underlying gross deletions in patients with primary immunodeficiency.
X 连锁无丙种球蛋白血症（XLA）患者可出现感觉神经性耳聋。这可能是由于大片段缺失引起的，不仅涉及布鲁顿酪氨酸激酶（BTK）基因，还涉及 TIMM8A 基因突变，这是 Mohr-Tranebjærg 综合征（MTS）的基础。我们分析了 3 例 XLA-MTS 患者中观察到的基因组断裂点，并将这些断裂点与 XLA 患者的缺失断裂点进行了比较。患者 1 存在 63kb 的缺失，BTK 的内含子 15 和 TAF7L 的上游 4kb 处存在断裂点。患者 2 和 3 存在包含 BTK、TIMM8A、TAF7L 和 DRP2 的 149.7 和 196kb 缺失。患者 1 和 3 的断裂点位于 Alu 和内源性逆转录病毒（ERV）重复序列中，而患者 2 的断裂点未显示转座元件的参与。对文献中 XLA 和 XLA-MTS 患者大片段缺失大小和转座元件参与的比较表明，较小缺失（<10kb）中 Alu 元件的优先参与。这些结果进一步揭示了原发性免疫缺陷患者大片段缺失的分子机制。
