Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly-progressing radiosensitive-severe combined immunodeficiency

Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly-progressing radiosensitive-severe combined immunodeficiency

Copyright © 2015 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 160(2015), 2 vom: 23. Okt., Seite 255-60
1. Verfasser: Tamura, Shinobu (VerfasserIn)
Weitere Verfasser: Higuchi, Kohei, Tamaki, Masaharu, Inoue, Chizuko, Awazawa, Ryoko, Mitsuki, Noriko, Nakazawa, Yuka, Mishima, Hiroyuki, Takahashi, Kenzo, Kondo, Osamu, Imai, Kohsuke, Morio, Tomohiro, Ohara, Osamu, Ogi, Tomoo, Furukawa, Fukumi, Inoue, Masami, Yoshiura, Koh-ichiro, Kanazawa, Nobuo
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2015
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Case Reports Journal Article Research Support, Non-U.S. Gov't DNA ligase IV Hematopoietic stem cell transplantation LIG4 syndrome Severe combined immunodeficiency TREC/KREC Whole exome sequencing LIG4 protein, human mehr... DNA Ligases EC 6.5.1.- DNA Ligase ATP EC 6.5.1.1
Beschreibung
Zusammenfassung:Copyright © 2015 Elsevier Inc. All rights reserved.
We herein describe a case of a 17-year-old boy with intractable common warts, short stature, microcephaly and slowly-progressing pancytopenia. Simultaneous quantification of T-cell receptor recombination excision circles (TREC) and immunoglobulin κ-deleting recombination excision circles (KREC) suggested very poor generation of both T-cells and B-cells. By whole exome sequencing, novel compound heterozygous mutations were identified in the patient's DNA ligase IV (LIG4) gene. The diagnosis of LIG4 syndrome was confirmed by delayed DNA double-strand break repair kinetics in γ-irradiated fibroblasts from the patient and their restoration by an introduction of wild-type LIG4. Although the patient received allogeneic hematopoietic stem cell transplantation from his haploidentical mother, he unfortunately expired due to an insufficiently reconstructed immune system. An earlier definitive diagnosis using TREC/KREC quantification and whole exome sequencing would thereby allow earlier intervention, which would be essential for improving long-term survival in similar cases with slowly-progressing LIG4 syndrome masked in adolescents
Beschreibung:Date Completed 15.12.2015
Date Revised 25.11.2016
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2015.07.004