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A Novel Homozygous Variant (C.5876T > C: P. Leu1959pro) in Dysf Segregates With Limb-Girdle Muscular Dystrophy: A Case Report Publisher Pubmed



Hesami H1 ; Ghasemi S1 ; Houshmand G1 ; Nilipour Y3, 4 ; Hesami M1 ; Biglari A5 ; Nafissi S4 ; Maleki M2 ; Kalayinia S2
Authors
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Authors Affiliations
  1. 1. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Pediatric Pathology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: BMC Musculoskeletal Disorders Published:2024


Abstract

Background: Limb girdle muscular dystrophies (LGMDs) constitute a heterogeneous group of neuromuscular disorders with a very variable clinical presentation and overlapping traits. The clinical symptoms of LGMD typically appear in adolescence or early adulthood. Genetic variation in the dysferlin gene (DYSF) has been associated with LGMD. Methods: We characterized a recessive LGMD in a young adult from consanguineous Irani families using whole-exome sequencing (WES) technology. Sanger sequencing was performed to verify the identified variant. Computational modeling and protein-protein docking were used to investigate the impact of the variant on the structure and function of the DYSF protein. Results: By WES, we identified a novel homozygous missense variant in DYSF (NM_003494.4: c.5876T > C: p. Leu1959Pro) previously been associated with LGMD phenotypes. Conclusions: The identification and validation of new pathogenic DYSF variant in the present study further highlight the importance of this gene in LGMD. © The Author(s) 2024.
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