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Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype

BACKGROUND: Dystrophinopathies are X‐linked recessive conditions caused by pathogenic variants in the dystrophin (DMD) gene. In a family that included two boys with Becker muscular dystrophy (BMD) due to a DMD deletion of exons 45–47, maternal carrier testing unexpectedly identified biallelic DMD de...

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Autores principales: Ulm, Elizabeth A., Nagaraj, Chinmayee B., Tian, Cuixia, Smolarek, Teresa A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834199/
https://www.ncbi.nlm.nih.gov/pubmed/36424846
http://dx.doi.org/10.1002/mgg3.2088
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author Ulm, Elizabeth A.
Nagaraj, Chinmayee B.
Tian, Cuixia
Smolarek, Teresa A.
author_facet Ulm, Elizabeth A.
Nagaraj, Chinmayee B.
Tian, Cuixia
Smolarek, Teresa A.
author_sort Ulm, Elizabeth A.
collection PubMed
description BACKGROUND: Dystrophinopathies are X‐linked recessive conditions caused by pathogenic variants in the dystrophin (DMD) gene. In a family that included two boys with Becker muscular dystrophy (BMD) due to a DMD deletion of exons 45–47, maternal carrier testing unexpectedly identified biallelic DMD deletions of exons 45–47 and 49–51. METHODS: The patient's mild phenotype in the setting of biallelic DMD variants prompted further investigation of the exon 49–51 deletion in particular, via literature review and retrospective chart review of patients who have been evaluated in our institution's comprehensive neuromuscular center and/or diagnosed in our clinical genetic testing laboratory. RESULTS: To our knowledge, this is only the fifth case of confirmed biallelic DMD variants in a female. In males, the DMD exon 49–51 deletion appears to result in a mild BMD phenotype with low or normal creatine kinase levels. This deletion comprised 19% (4/21) of dystrophinopathies diagnosed by chromosomal microarray (CMA) in males during the past ten years in our clinical laboratory. Most individuals identified by chart review were diagnosed through CMA, despite the fact that microarray was genome‐wide and not DMD‐specific. This case raised important genetic counseling issues. CONCLUSION: The DMD exon 49–51 deletion appears to cause a variable but generally mild BMD phenotype. Its relatively frequent detection by CMA suggests it may be underdiagnosed.
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spelling pubmed-98341992023-01-13 Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype Ulm, Elizabeth A. Nagaraj, Chinmayee B. Tian, Cuixia Smolarek, Teresa A. Mol Genet Genomic Med Original Articles BACKGROUND: Dystrophinopathies are X‐linked recessive conditions caused by pathogenic variants in the dystrophin (DMD) gene. In a family that included two boys with Becker muscular dystrophy (BMD) due to a DMD deletion of exons 45–47, maternal carrier testing unexpectedly identified biallelic DMD deletions of exons 45–47 and 49–51. METHODS: The patient's mild phenotype in the setting of biallelic DMD variants prompted further investigation of the exon 49–51 deletion in particular, via literature review and retrospective chart review of patients who have been evaluated in our institution's comprehensive neuromuscular center and/or diagnosed in our clinical genetic testing laboratory. RESULTS: To our knowledge, this is only the fifth case of confirmed biallelic DMD variants in a female. In males, the DMD exon 49–51 deletion appears to result in a mild BMD phenotype with low or normal creatine kinase levels. This deletion comprised 19% (4/21) of dystrophinopathies diagnosed by chromosomal microarray (CMA) in males during the past ten years in our clinical laboratory. Most individuals identified by chart review were diagnosed through CMA, despite the fact that microarray was genome‐wide and not DMD‐specific. This case raised important genetic counseling issues. CONCLUSION: The DMD exon 49–51 deletion appears to cause a variable but generally mild BMD phenotype. Its relatively frequent detection by CMA suggests it may be underdiagnosed. John Wiley and Sons Inc. 2022-11-24 /pmc/articles/PMC9834199/ /pubmed/36424846 http://dx.doi.org/10.1002/mgg3.2088 Text en © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Ulm, Elizabeth A.
Nagaraj, Chinmayee B.
Tian, Cuixia
Smolarek, Teresa A.
Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype
title Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype
title_full Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype
title_fullStr Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype
title_full_unstemmed Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype
title_short Identification of Biallelic dystrophin gene variants during maternal carrier testing for Becker muscular dystrophy and review of the DMD exon 49–51 deletion phenotype
title_sort identification of biallelic dystrophin gene variants during maternal carrier testing for becker muscular dystrophy and review of the dmd exon 49–51 deletion phenotype
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834199/
https://www.ncbi.nlm.nih.gov/pubmed/36424846
http://dx.doi.org/10.1002/mgg3.2088
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