背景:Dysferlinopathy是一组由DYSF基因突变引起的表型异质性遗传性疾病。早期挛缩被认为是罕见的,和僵硬的脊柱综合征在发育异常疾病以前只报道过一次。
方法:我们描述了一名23岁的Miyoshi肌病患者,脊柱僵硬,多处挛缩,一种罕见的表型变异。该疾病在患者13岁时首次出现,随着腓肠肌的疲劳和跟腱的明显挛缩的发展,手指的屈肌,和脚趾的伸肌,其次是大关节和脊柱受累。磁共振成像显示,大腿和小腿后部肌肉有结缔组织和脂肪替代的迹象。大腿前肌群和内侧肌群有水肿,小腿,和背部的多裂肌。全基因组测序揭示了先前描述的DYSF基因在外显子39(c.4282C>T)和内含子51(c.5785-824C>T)中的突变。免疫组织化学分析和蛋白质印迹显示肌纤维中完全不存在dysferlin蛋白表达。
结论:该病例扩大了异常铁蛋白病的临床和表型相关性的范围,并补充了脊柱强直的诊断研究。
BACKGROUND: Dysferlinopathy is a phenotypically heterogeneous group of hereditary diseases caused by mutations in the DYSF gene. Early contractures are considered rare, and rigid spine syndrome in dysferlinopathy has been previously reported only once.
METHODS: We describe a 23-year-old patient with Miyoshi myopathy with a rigid spine and multiple contractures, a rare phenotypic variant. The disease first manifested when the patient was 13 years old, with fatigue of the gastrocnemius muscles and the development of pronounced contractures of the Achilles tendons, flexors of the fingers, and extensors of the toes, followed by the involvement of large joints and the spine. Magnetic resonance imaging revealed signs of connective tissue and fatty replacement of the posterior muscles of the thighs and lower legs. Edema was noted in the anterior and medial muscle groups of the thighs, lower legs, and the multifidus muscle of the back. Whole genome sequencing revealed previously described mutations in the DYSF gene in exon 39 (c.4282 C > T) and intron 51 (c.5785-824 C > T). An immunohistochemical analysis and Western blot showed the complete absence of dysferlin protein expression in the muscle fibers.
CONCLUSIONS: This
case expands the range of clinical and phenotypic correlations of dysferlinopathy and complements the diagnostic search for spine rigidity.