A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing
Abstract Background Dysferlinopathies are autosomal recessive muscular dystrophies resulting from defects in DYSF (MIM: 603009), which is located on chromosome 2p13 and encodes the dysferlin protein. Methods We performed exome sequencing and subsequent trio‐based analysis in a family with dysferlino...
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2110 |
| _version_ | 1797903422457905152 |
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| author | Huan Li Liang Wang Cheng Zhang |
| author_facet | Huan Li Liang Wang Cheng Zhang |
| author_sort | Huan Li |
| collection | DOAJ |
| description | Abstract Background Dysferlinopathies are autosomal recessive muscular dystrophies resulting from defects in DYSF (MIM: 603009), which is located on chromosome 2p13 and encodes the dysferlin protein. Methods We performed exome sequencing and subsequent trio‐based analysis in a family with dysferlinopathy. Results We report a young patient presenting with hyperCKemia and mild muscle weakness of the lower limbs. Exome sequencing of the proband revealed a homozygous frameshift mutation, NM_001130987.2:c.1471dupA(p.M491Nfs*15), in DYSF. The father was heterozygous for the mutation and the mother did not carry the mutation, as determined by genetic analyses, exome sequencing of parental samples, and a trio‐based analysis. Further analysis revealed that the DYSF gene was not deleted; instead, the entire chromosome 2 of the proband was inherited from the father. Thus, the child had paternal uniparental isodisomy for chromosome 2 (uniparental disomy [UPD]2 pat). Conclusion We report the first case of dysferlinopathy caused by paternal isodisomy for chromosome 2. Furthermore, our findings highlight the importance of exome sequencing of the proband and parents and trio analyses in clinical settings, particularly when Mendelian inheritance cannot be confirmed, to identify the presence of UPD and to rule out large pathogenic deletions. |
| first_indexed | 2024-04-10T09:32:41Z |
| format | Article |
| id | doaj.art-fef627304280450e8efeff5837ed78ce |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-10T09:32:41Z |
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| spelling | doaj.art-fef627304280450e8efeff5837ed78ce2023-02-18T19:05:43ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-02-01112n/an/a10.1002/mgg3.2110A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencingHuan Li0Liang Wang1Cheng Zhang2Department of Neurology, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaAbstract Background Dysferlinopathies are autosomal recessive muscular dystrophies resulting from defects in DYSF (MIM: 603009), which is located on chromosome 2p13 and encodes the dysferlin protein. Methods We performed exome sequencing and subsequent trio‐based analysis in a family with dysferlinopathy. Results We report a young patient presenting with hyperCKemia and mild muscle weakness of the lower limbs. Exome sequencing of the proband revealed a homozygous frameshift mutation, NM_001130987.2:c.1471dupA(p.M491Nfs*15), in DYSF. The father was heterozygous for the mutation and the mother did not carry the mutation, as determined by genetic analyses, exome sequencing of parental samples, and a trio‐based analysis. Further analysis revealed that the DYSF gene was not deleted; instead, the entire chromosome 2 of the proband was inherited from the father. Thus, the child had paternal uniparental isodisomy for chromosome 2 (uniparental disomy [UPD]2 pat). Conclusion We report the first case of dysferlinopathy caused by paternal isodisomy for chromosome 2. Furthermore, our findings highlight the importance of exome sequencing of the proband and parents and trio analyses in clinical settings, particularly when Mendelian inheritance cannot be confirmed, to identify the presence of UPD and to rule out large pathogenic deletions.https://doi.org/10.1002/mgg3.2110dysferlinopathyexome sequencingmuscular dystrophypaternal isodisomy |
| spellingShingle | Huan Li Liang Wang Cheng Zhang A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing Molecular Genetics & Genomic Medicine dysferlinopathy exome sequencing muscular dystrophy paternal isodisomy |
| title | A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing |
| title_full | A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing |
| title_fullStr | A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing |
| title_full_unstemmed | A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing |
| title_short | A rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing |
| title_sort | rare case of dysferlinopathy with paternal isodisomy for chromosome 2 determined by exome sequencing |
| topic | dysferlinopathy exome sequencing muscular dystrophy paternal isodisomy |
| url | https://doi.org/10.1002/mgg3.2110 |
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