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Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure

BACKGROUND: DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia...

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Autores principales: Gruhn, Bernd, Seidel, Joerg, Zintl, Felix, Varon, Raymonda, Tönnies, Holger, Neitzel, Heidemarie, Bechtold, Astrid, Hoehn, Holger, Schindler, Detlev
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781429/
https://www.ncbi.nlm.nih.gov/pubmed/17224058
http://dx.doi.org/10.1186/1750-1172-2-5
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author Gruhn, Bernd
Seidel, Joerg
Zintl, Felix
Varon, Raymonda
Tönnies, Holger
Neitzel, Heidemarie
Bechtold, Astrid
Hoehn, Holger
Schindler, Detlev
author_facet Gruhn, Bernd
Seidel, Joerg
Zintl, Felix
Varon, Raymonda
Tönnies, Holger
Neitzel, Heidemarie
Bechtold, Astrid
Hoehn, Holger
Schindler, Detlev
author_sort Gruhn, Bernd
collection PubMed
description BACKGROUND: DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion. METHODS: We describe a patient with pre- and postnatal growth retardation and dysmorphic facial features in whom the diagnoses of Seckel-, Dubowitz-, and Nijmegen breakage syndrome were variably considered. Cellular radiosensitivity in the absence of clinical manifestations of Ataxia telangiectasia lead to the diagnosis of DNA ligase IV (LIG4) deficiency syndrome, confirmed by compound heterozygous mutations in the LIG4 gene. At age 11, after a six year history of progressive bone marrow failure and increasing transfusion dependency the patient was treated with matched sibling donor hematopoetic stem cell transplantation (HSCT) using a fludarabine-based conditioning regimen without irradiation. RESULTS: The post-transplantation course was uneventful with rapid engraftment leading to complete and stable chimerism. Now at age 16, the patient has gained weight and is in good clinical condition. CONCLUSION: HSCT using mild conditioning without irradiation qualifies as treatment of choice in LIG4-deficient patients who have a matched sibling donor.
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spelling pubmed-17814292007-01-25 Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure Gruhn, Bernd Seidel, Joerg Zintl, Felix Varon, Raymonda Tönnies, Holger Neitzel, Heidemarie Bechtold, Astrid Hoehn, Holger Schindler, Detlev Orphanet J Rare Dis Case Report BACKGROUND: DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion. METHODS: We describe a patient with pre- and postnatal growth retardation and dysmorphic facial features in whom the diagnoses of Seckel-, Dubowitz-, and Nijmegen breakage syndrome were variably considered. Cellular radiosensitivity in the absence of clinical manifestations of Ataxia telangiectasia lead to the diagnosis of DNA ligase IV (LIG4) deficiency syndrome, confirmed by compound heterozygous mutations in the LIG4 gene. At age 11, after a six year history of progressive bone marrow failure and increasing transfusion dependency the patient was treated with matched sibling donor hematopoetic stem cell transplantation (HSCT) using a fludarabine-based conditioning regimen without irradiation. RESULTS: The post-transplantation course was uneventful with rapid engraftment leading to complete and stable chimerism. Now at age 16, the patient has gained weight and is in good clinical condition. CONCLUSION: HSCT using mild conditioning without irradiation qualifies as treatment of choice in LIG4-deficient patients who have a matched sibling donor. BioMed Central 2007-01-15 /pmc/articles/PMC1781429/ /pubmed/17224058 http://dx.doi.org/10.1186/1750-1172-2-5 Text en Copyright © 2007 Gruhn et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Report
Gruhn, Bernd
Seidel, Joerg
Zintl, Felix
Varon, Raymonda
Tönnies, Holger
Neitzel, Heidemarie
Bechtold, Astrid
Hoehn, Holger
Schindler, Detlev
Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
title Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
title_full Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
title_fullStr Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
title_full_unstemmed Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
title_short Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure
title_sort successful bone marrow transplantation in a patient with dna ligase iv deficiency and bone marrow failure
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781429/
https://www.ncbi.nlm.nih.gov/pubmed/17224058
http://dx.doi.org/10.1186/1750-1172-2-5
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