Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy
Abstract Background Limb-girdle muscular dystrophies (LGMDs) constitute a genetically diverse group of disorders characterized by progressive proximal muscle weakness and atrophy. Despite advances in genetic diagnostics, numerous cases remain unresolved due to extensive genetic heterogeneity, emphas...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | Human Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40246-025-00809-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849342673606934528 |
|---|---|
| author | Abdelaziz Tlili Abdullah Al Mutery |
| author_facet | Abdelaziz Tlili Abdullah Al Mutery |
| author_sort | Abdelaziz Tlili |
| collection | DOAJ |
| description | Abstract Background Limb-girdle muscular dystrophies (LGMDs) constitute a genetically diverse group of disorders characterized by progressive proximal muscle weakness and atrophy. Despite advances in genetic diagnostics, numerous cases remain unresolved due to extensive genetic heterogeneity, emphasizing the necessity for continued identification of novel pathogenic variants. Results Using whole-exome sequencing (WES) in a Saudi family affected by autosomal recessive LGMD, we identified a novel homozygous frameshift mutation (c.891delT; p.Ala298ArgfsTer64) in the TRIM72 (MG53) gene, which we propose as a strong candidate gene for LGMD. Segregation analysis via Sanger sequencing confirmed that the variant co-segregated precisely with the disease phenotype and was absent in ethnically matched control cohorts. TRIM72 encodes a muscle-specific E3 ubiquitin ligase involved in sarcolemmal membrane repair, critical for maintaining muscle cell integrity. Functional parallels between TRIM72 and the LGMD-associated TRIM32, alongside corroborating evidence from animal models and cellular studies, support the candidacy of TRIM72 in LGMD pathogenesis. Conclusion Our findings identify TRIM72 as a novel candidate gene implicated in autosomal recessive LGMD, expanding the genetic spectrum of this heterogeneous disease. This discovery underscores the critical roles of TRIM family proteins in muscle pathology and reinforces the value of advanced genetic sequencing methodologies in diagnosing unresolved muscular dystrophy cases. |
| format | Article |
| id | doaj-art-3b2b6896839f4d3ca3aff20500ba50bd |
| institution | Kabale University |
| issn | 1479-7364 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj-art-3b2b6896839f4d3ca3aff20500ba50bd2025-08-20T03:43:20ZengBMCHuman Genomics1479-73642025-08-011911610.1186/s40246-025-00809-7Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophyAbdelaziz Tlili0Abdullah Al Mutery1Department of Applied Biology, College of Sciences, University of SharjahDepartment of Applied Biology, College of Sciences, University of SharjahAbstract Background Limb-girdle muscular dystrophies (LGMDs) constitute a genetically diverse group of disorders characterized by progressive proximal muscle weakness and atrophy. Despite advances in genetic diagnostics, numerous cases remain unresolved due to extensive genetic heterogeneity, emphasizing the necessity for continued identification of novel pathogenic variants. Results Using whole-exome sequencing (WES) in a Saudi family affected by autosomal recessive LGMD, we identified a novel homozygous frameshift mutation (c.891delT; p.Ala298ArgfsTer64) in the TRIM72 (MG53) gene, which we propose as a strong candidate gene for LGMD. Segregation analysis via Sanger sequencing confirmed that the variant co-segregated precisely with the disease phenotype and was absent in ethnically matched control cohorts. TRIM72 encodes a muscle-specific E3 ubiquitin ligase involved in sarcolemmal membrane repair, critical for maintaining muscle cell integrity. Functional parallels between TRIM72 and the LGMD-associated TRIM32, alongside corroborating evidence from animal models and cellular studies, support the candidacy of TRIM72 in LGMD pathogenesis. Conclusion Our findings identify TRIM72 as a novel candidate gene implicated in autosomal recessive LGMD, expanding the genetic spectrum of this heterogeneous disease. This discovery underscores the critical roles of TRIM family proteins in muscle pathology and reinforces the value of advanced genetic sequencing methodologies in diagnosing unresolved muscular dystrophy cases.https://doi.org/10.1186/s40246-025-00809-7Limb-girdle muscular dystrophiesAutosomal recessiveTRIM72 geneFrameshift mutation |
| spellingShingle | Abdelaziz Tlili Abdullah Al Mutery Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy Human Genomics Limb-girdle muscular dystrophies Autosomal recessive TRIM72 gene Frameshift mutation |
| title | Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy |
| title_full | Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy |
| title_fullStr | Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy |
| title_full_unstemmed | Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy |
| title_short | Whole-exome sequencing identifies TRIM72 as a candidate gene for autosomal recessive limb-girdle muscular dystrophy |
| title_sort | whole exome sequencing identifies trim72 as a candidate gene for autosomal recessive limb girdle muscular dystrophy |
| topic | Limb-girdle muscular dystrophies Autosomal recessive TRIM72 gene Frameshift mutation |
| url | https://doi.org/10.1186/s40246-025-00809-7 |
| work_keys_str_mv | AT abdelaziztlili wholeexomesequencingidentifiestrim72asacandidategeneforautosomalrecessivelimbgirdlemusculardystrophy AT abdullahalmutery wholeexomesequencingidentifiestrim72asacandidategeneforautosomalrecessivelimbgirdlemusculardystrophy |