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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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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author Jean‐Pierre de Villartay
author_facet Jean‐Pierre de Villartay
author_sort Jean‐Pierre de Villartay
collection DOAJ
description 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.
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spelling doaj-art-fdb39f5a94e8484b9cdcbbdaf09de7c12025-08-20T03:46:24ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842015-05-017786286410.15252/emmm.201505307When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencingJean‐Pierre de Villartay0INSERM UMR1163, Laboratory of Genome Dynamics in the Immune System (DGSI)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.https://doi.org/10.15252/emmm.201505307
spellingShingle Jean‐Pierre de Villartay
When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencing
EMBO Molecular Medicine
title When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencing
title_full When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencing
title_fullStr When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencing
title_full_unstemmed When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencing
title_short When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole‐exome sequencing
title_sort when natural mutants do not fit our expectations the intriguing case of patients with xrcc4 mutations revealed by whole exome sequencing
url https://doi.org/10.15252/emmm.201505307
work_keys_str_mv AT jeanpierredevillartay whennaturalmutantsdonotfitourexpectationstheintriguingcaseofpatientswithxrcc4mutationsrevealedbywholeexomesequencing