Duchenne Muscular Dystrophy in Two Half-Brothers Due to Inherited 306 Kb Inverted Insertion of 10p15.1 into Intron 44 of the Dp427m Transcript of the DMD Gene

Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by the absence of a fully functional dystrophin protein in myocytes. In skeletal muscle, the lack of dystrophin ultimately results in muscle wasting and the replacement of myocytes with fatty or fibrous tissues. In the heart, cardio...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-11, Vol.25 (22), p.11922
Main Authors: Jepsen, Wayne M, Fazenbaker, Andrew, Ramsey, Keri, Bonfitto, Anna, Naymik, Marcus, Turner, Bryce, Sloan, Jennifer, Tiwari, Nishant, Bernes, Saunder M, Neilson, Derek E, Sanchez-Castillo, Meredith, Huentelman, Matt J, Narayanan, Vinodh
Format: Article
Language:English
Subjects:
Biopsy
Case Report
Causes of
Chromosomes
Chromosomes, Human, Pair 10 - genetics
Duchenne muscular dystrophy
Dystrophin - genetics
Exons - genetics
Families & family life
Fractures
Genes
Genetic aspects
Genetic testing
Genomes
Health aspects
Humans
Introns - genetics
Laboratories
Male
Muscular dystrophy
Muscular Dystrophy, Duchenne - genetics
Mutagenesis, Insertional
Pathology
Pediatric research
Proteins
RNA splicing
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Summary:Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by the absence of a fully functional dystrophin protein in myocytes. In skeletal muscle, the lack of dystrophin ultimately results in muscle wasting and the replacement of myocytes with fatty or fibrous tissues. In the heart, cardiomyocytes eventually fail and cause fatal cardiomyopathy. We present a case of a male patient and his younger brother with a maternally inherited inverted insertion of approximately 306 kb of chromosome 10 in the deep intronic region between exons 44 and 45 of the gene, leading to Duchenne muscular dystrophy. Chromosomal microarray, comprehensive muscular dystrophy genetic testing, and whole exome sequencing were negative. Targeted transcriptome RNA sequencing at an external lab showed no aberrant splicing. Research whole genome sequencing identified the copy number gain and insertion. Subsequent reanalysis of the RNA sequencing data showed possible aberrant splicing involving exons 44-45, and research RNA sequencing revealed a fusion between the gene on the minus strand of chromosome X and the gene on the plus strand of chromosome 10. We demonstrate that whole genome sequencing can be valuable for identifying intronic events in the gene previously undetected or not reported by traditional clinical testing.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms252211922