Abstract
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.
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Acknowledgements
This study was supported in part by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by a grant from the Ministry of Health, Labour and Welfare of Japan. We thank Chikako Sakai, Hitoshi Moriuchi and Noboru Hosogai for their excellent technical assistance. We are also grateful to the support, cooperation and trust of the patients and their families.
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Arai, T., Zhao, M., Kanegane, H. et al. Genetic analysis of contiguous X-chromosome deletion syndrome encompassing the BTK and TIMM8A genes. J Hum Genet 56, 577–582 (2011). https://doi.org/10.1038/jhg.2011.61
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DOI: https://doi.org/10.1038/jhg.2011.61
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