DOI: 10.1007/s12017-016-8440-8 Pages: 161-174
Article Type: Original Paper

Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia

1. University of Granada, Health Sciences Technology Park, Institute of Biopathology and Regenerative Medicine, Center for Biomedical Research

2. Health Sciences Technology Park, Genomic Unit, Center Pfizer-University of Granada-Junta de Andalucia for Genomics and Oncological Research (GENYO)

3. University of Córdoba, Service of Immunology and Department of Cell Biology and Immunology, “Reina Sofia” University Hospital

4. University of Granada, Service of Pediatrics, “Virgen de las Nieves” University Hospital

5. University of Granada, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada University Hospitals

Correspondence to:
Ignacio J. Molina



Ataxia-telangiectasia is a multisystemic disease with severe neurological affectation, immunodeficiency and telangiectasia. The disorder is caused by alterations in the ATM gene, whose size and complexity make molecular diagnosis difficult. We designed a target-enrichment next-generation sequencing strategy to characterize 28 patients from several regions of Spain. This approach allowed us to identify gene variants affecting function in 54 out of the 56 alleles analyzed, although the two unresolved alleles belong to brothers. We found 28 ATM gene mutations, of which 10 have not been reported. A total of 171 gene variants not affecting function were also found, of which 22 are reported to predispose to disease. Interestingly, all Roma (Spanish Gypsies) patients are homozygous for the same mutation and share the H3 ATM haplotype, which is strong evidence of a founder effect in this population. In addition, we generated a panel of 27 primary T cell lines from A-T patients, which revealed significant expression of ATM in two patients and traces of the protein in nine more. None of them retained residual ATM activity, and almost all T cell lines show increased or intermediate radiosensitivity.

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  • Accepted: Sep 10, 2016
  • Online: Sep 23, 2016

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