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.

Additional Metadata
Keywords Alu, BTK, Mohr-Tranebjærg syndrome, TIMM8A, X-linked agammaglobulinemia
Persistent URL dx.doi.org/10.1038/jhg.2011.61, hdl.handle.net/1765/34367
Citation
Arai, T., Zhao, M., Kanegane, H., van Zelm, M.C., Futatani, T., Yamada, M., … Oh-Ishi, T.. (2011). Genetic analysis of contiguous X-chromosome deletion syndrome encompassing the BTK and TIMM8A genes. Journal of Human Genetics, 56(8), 577–582. doi:10.1038/jhg.2011.61