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01-03-2017 | Original Paper

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

Authors: Diana Carranza, Ana Karina Vega, Sara Torres-Rusillo, Enrique Montero, Luis Javier Martinez, Manuel Santamaría, Juan Luis Santos, Ignacio J. Molina

Published in: NeuroMolecular Medicine | Issue 1/2017

Abstract

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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Title: Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia
Authors: Diana Carranza
Ana Karina Vega
Sara Torres-Rusillo
Enrique Montero
Luis Javier Martinez
Manuel Santamaría
Juan Luis Santos
Ignacio J. Molina
Publication date: 01-03-2017
Publisher: Springer US
Published in: NeuroMolecular Medicine / Issue 1/2017
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-016-8440-8

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

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