Ataxia Telangiectasia is a complex multisystem disorder characterized by progressive neurologic impairment, altered balance, variable immunodeficiency with susceptibility to upper respiratory tract infections, impaired organ maturation, ocular and cutaneous telangiectasia and predisposition to malignancy. Malignancy usually involves the lymphatic system (i.e., lymphomas) and blood-forming organs (i.e., leukemia) as well as the brain. It is a primary immunodeficiency of B and T cells caused by a mutation in genes encoding DNA repair enzymes. This disease has a very heterogeneous presentation and genetic background, as shown by the existence of 4 complementation groups (A,C,D,E). As well, there is a variable rate of progression leading to death often by early adulthood. It is inherited in an autosomal recessive manner.
The Igenomix Ataxia Telangiectasia Precision Panel can be as a tool for an accurate diagnosis as well as differential diagnosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved, and their high or intermediate penetrance.
The clinical utility of this panel is:
GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
ATM | Ataxia-Telangiectasia, | AD,AR | 99.93 | 1608 of 1632 |
MRE11 | Ataxia-Telangiectasia- | AR | 99.95 | NA of NA |
NBN | Aplastic Anemia, | AR,MU,P | 100 | 200 of 200 |
PCNA | Ataxia-Telangiectasia- | AR | 99.92 | 1 of 1 |
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial
** HGMD: Number of clinically relevant mutations according to HGMD
Soresina, A., Meini, A., Lougaris, V., Cattaneo, G., Pellegrino, S., & Piane, M. et al. (2008). Different Clinical and Immunological Presentation of Ataxia-Telangiectasia within the Same Family. Neuropediatrics, 39(1), 43-45. doi: 10.1055/s-2008-1076736
McGrath-Morrow, S. A., Ndeh, R., Helmin, K. A., Khuder, B., Rothblum-Oviatt, C., Collaco, J. M., Wright, J., Reyfman, P. A., Lederman, H. M., & Singer, B. D. (2020). DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype. Scientific reports, 10(1), 7479. https://doi.org/10.1038/s41598-020-64514-2
van Os, N., Chessa, L., Weemaes, C., van Deuren, M., Fiévet, A., van Gaalen, J., Mahlaoui, N., Roeleveld, N., Schrader, C., Schindler, D., Taylor, A., Van de Warrenburg, B., Dörk, T., & Willemsen, M. (2019). Genotype-phenotype correlations in ataxia telangiectasia patients with ATM c.3576G>A and c.8147T>C mutations. Journal of medical genetics, 56(5), 308–316. https://doi.org/10.1136/jmedgenet-2018-105635
Verhagen, M. (2011). 1FC3.3 The amounts of ATM protein and residual kinase activity predict the phenotype in Ataxia-Telangiectasia: A genotype – phenotype study. European Journal Of Paediatric Neurology, 15, S15. doi: 10.1016/s1090-3798(11)70055-1
Liu, X., Wang, T., Huang, X., Zhou, H., Luan, X., & Shen, J. et al. (2016). Novel ATM mutations with ataxia-telangiectasia. Neuroscience Letters, 611, 112-115. doi: 10.1016/j.neulet.2015.11.036
