When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencing

Abstract Mutations in the XRCC4 gene have been recently identified through whole‐exome sequencing (WES). While the overall clinical presentation of the patients (severe short stature, microcephaly, gonadal failure) generally conforms with what is expected for the defect of a critical non‐homologous...

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Bibliographic Details
Main Author: Jean‐Pierre de Villartay
Format: Article
Language:English
Published: Springer Nature 2015-05-01
Series:EMBO Molecular Medicine
Online Access:https://doi.org/10.15252/emmm.201505307
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Summary:Abstract Mutations in the XRCC4 gene have been recently identified through whole‐exome sequencing (WES). While the overall clinical presentation of the patients (severe short stature, microcephaly, gonadal failure) generally conforms with what is expected for the defect of a critical non‐homologous end‐joining (NHEJ) DNA repair factor, the absence of consequence on the proper development of the immune system is rather surprising, given the role of NHEJ in V(D)J recombination. Several hypotheses can be envisioned to explain this discrepancy. Overall, these findings highlight the power of WES in identifying new molecular causes for human diseases while providing with new exciting scientific question to address.
ISSN:1757-4676
1757-4684