一个新的 DYSF 纯合变异（c.5876T>C：p.Leu1959Pro）与肢带型肌营养不良症相关：一例报告。
A novel homozygous variant (c.5876T > C: p. Leu1959Pro) in DYSF segregates with limb-girdle muscular dystrophy: a case report.
机构信息
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Pediatric Pathology Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
BMC Musculoskelet Disord. 2024 Mar 27;25(1):241. doi: 10.1186/s12891-024-07354-9.
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.
背景
肢带型肌营养不良症（LGMDs）是一组异质性神经肌肉疾病，临床表现非常多样，具有重叠特征。LGMD 的临床症状通常在青少年或成年早期出现。肌营养不良蛋白基因（DYSF）的遗传变异与 LGMD 有关。
方法
我们使用外显子组测序（WES）技术对来自近亲伊朗家庭的年轻成人进行隐性 LGMD 进行了特征描述。通过 Sanger 测序对鉴定出的变异进行了验证。通过计算建模和蛋白质-蛋白质对接，研究了该变异对 DYSF 蛋白结构和功能的影响。
结果
通过 WES，我们在 DYSF 中发现了一个新的纯合错义变异（NM_003494.4: c.5876T>C: p.Leu1959Pro），之前与 LGMD 表型有关。
结论
本研究中对新的致病性 DYSF 变异的鉴定和验证进一步强调了该基因在 LGMD 中的重要性。
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