Miyoshi Muscular Dystrophy Due to Novel Splice Site Variants in DYSF Gene.
Miyoshi Muscular Dystrophy Due to Novel Splice Site Variants in DYSF Gene.
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DOI：
10.1177/2329048x221140298
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发表时间：
2022-01
影响因子：
--
通讯作者：
Veerapandiyan, Aravindhan
中科院分区：
文献类型：
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作者：
Bryant, Grace;Moore, Steven A;Nix, James S;Rice, Grace;Gokden, Murat;Veerapandiyan, Aravindhan
异常铁蛋白病是一组由编码异常铁蛋白的DYSF（营养不良相关的铁-1样）基因的致病性变异引起的表型异质性疾病。表型谱包括三吉氏肌营养不良症（MMD），四肢带状肌营养不良R2型，远端肌病胫前发病，和孤立的高血氧症。烟雾病的特征是肌肉无力和萎缩，主要影响小腿肌肉，症状发作在14至40岁之间。异铁蛋白病没有明确的表型-基因型相关性。我们描述了一位15岁的女孩，她的表型与烟雾病一致。然而，她最初因假定为多肌炎而接受治疗，但未见好转。随后的基因检测发现了DYSF的两个新变异：第30外显子的c.3225dup （p.Gly1076Trpfs*38）和第30内含子的c.3349-2A > G（剪接受体）。免疫染色和免疫印迹法在肌肉活检中未检测到异常铁蛋白，这一结果与异常铁蛋白病一致，支持DYSF变异的致病性。
Dysferlinopathies are a group of phenotypically heterogeneous disorders caused by pathogenic variants in the DYSF (DYStrophy-associated Fer-1-like) gene encoding dysferlin. The phenotypic spectrum includes Miyoshi muscular dystrophy (MMD), limb-girdle muscular dystrophy type R2, distal myopathy with anterior tibial onset, and isolated hyperCKemia. MMD is characterized by muscle weakness and atrophy predominantly affecting the calf muscles with symptoms onset between 14 and 40 years of age. There is no clear phenotype – genotype correlation for dysferlinopathy. We describe a 15-year-old girl who presented with a phenotype consistent with MMD. However, she was initially treated for presumed polymyositis without improvement. Subsequent genetic testing revealed two novel variants in DYSF: c.3225dup (p.Gly1076Trpfs*38) in exon 30 and c.3349-2A > G (Splice acceptor) in intron 30. No dysferlin was detected in a muscle biopsy using immunostains and western blots, a result consistent with dysferlinopathy that supports the pathogenicity of the DYSF variants.