Miyoshi myopathy patients with novel 5′ splicing donor site mutations showed different dysferlin immunostaining at the sarcolemma
Miyoshi myopathy patients with novel 5′ splicing donor site mutations showed different dysferlin immunostaining at the sarcolemma
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DOI：
10.1007/s00401-002-0593-x
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发表时间：
2002-12-01
影响因子：
12.7
通讯作者：
Osame, M
中科院分区：
文献类型：
--
作者：
Saito, A;Higuchi, I;Osame, M
我们分析了五例临床明确的宫本氏肌病的遗传和免疫学特征。肌肉标本的蛋白质印迹证实，所有患者都存在脱铁蛋白缺乏症。免疫组织化学显示，5例患者中有2例呈异铁蛋白免疫染色阳性。随后对这两名患者的deferlin基因进行的突变分析显示，两人都有新的5‘剪接供体位点突变。1例在1036+1外显子6剪接供体部位发生G-C纯合子替换的患者，肌膜功能障碍蛋白免疫染色呈斑片状。第2例同时存在1310+1外显子10剪接供体位点G-A杂合性替换和1939核苷酸C-G杂合性替换(导致外显子18酪氨酸522终止)的患者，肌膜和弥漫性胞浆无铁蛋白免疫染色均呈斑片状。与Becker肌营养不良相比，异铁蛋白染色阳性患者的临床病程和严重程度与阴性患者无明显差异。这些结果表明，deferlin基因的剪接突变可能有可能导致deferlin表达降低，但可能与较轻微的临床表型无关。
We analyzed five clinically defined cases of Miyoshi myopathy both genetically and immunologically. Western blot of muscle specimens confirmed that all of these patients had dysferlin deficiency. Immunohistochemistry revealed that two of the five patients showed positive dysferlin immunostaining. Subsequent mutation analysis of the dysferlin gene in these two patients revealed that both had novel 5' splicing donor site mutations. One patient with a homozygous G to C substitution at nucleotide 1036+1 exon 6 splicing donor site showed patchy sarcolemmal dysferlin immunostaining. The second patient with both a heterozygous G to A substitution at nucleotide 1310+1 exon 10 splicing donor site and a heterozygous C to G substitution at nucleotide 1939 (which induces Tyr 522 Stop of exon 18) showed both patchy sarcolemmal and diffuse cytoplasmic dysferlin immunostaining. In contrast to Becker muscular dystrophy, the clinical course and severity of dysferlin staining positive patients was not clearly different from negative patients. These results suggest that a splicing mutation of the dysferlin gene may have the potential to cause decreased dysferlin expression but may not be related to the milder clinical phenotype.