Fidzianska A, Morrone A, Pegoraro E, Ryniewicz B, Ilnicka A, Zammarchi E, Hoffman E P
Department of Neurology, Medical School, Polish Academy of Science, Warsaw.
Neuropediatrics. 1995 Jun;26(3):163-7. doi: 10.1055/s-2007-979747.
We report a 5-year-old girl with clinical symptoms of typical Duchenne muscular dystrophy in males. The girl showed dramatic elevations of serum creatine kinase, and muscle biopsy histopathology consistent with a severe dystrophic myopathy. Cytogenetic analysis revealed an X:22 translocation (46,X,t [X;22] [p21.2;11.2]). Dystrophin immunofluoresence studies showed strong membrane immunostaining of dystrophin with antibodies directed against the amino terminus of the protein, but vastly reduced immunostaining with carboxyl-terminal antibodies. Immunoblot studies showed a major immunoreactive protein of approximately 350 kDa at approximately 20% levels. Nested RT-PCR analysis of the dystrophin mRNA in the patient's muscle showed the RNA to be positive for primers covering the first 85% of the dystrophin coding sequence, and negative for the carboxyl-terminal 15%. Taken together, our data suggests that the translocation breakpoint occurs towards the 3' end of the gene. The translocated dystrophin gene is still expressed into a truncated dystrophin protein associated with the plasma membrane. Our results are consistent with the translocation resulting in a more stable abnormal dystrophin mRNA.
我们报告了一名5岁女童，她具有典型杜氏肌营养不良症男性患者的临床症状。该女童血清肌酸激酶显著升高，肌肉活检组织病理学显示符合严重营养不良性肌病。细胞遗传学分析显示存在X:22易位（46,X,t[X;22][p21.2;11.2]）。抗肌萎缩蛋白免疫荧光研究表明，针对该蛋白氨基末端的抗体可使抗肌萎缩蛋白在细胞膜上呈现强免疫染色，但针对羧基末端的抗体免疫染色则大幅减少。免疫印迹研究显示，主要免疫反应蛋白约为350 kDa，含量约为正常水平的20%。对患者肌肉中抗肌萎缩蛋白mRNA进行巢式逆转录聚合酶链反应（Nested RT-PCR）分析，结果显示，覆盖抗肌萎缩蛋白编码序列前85%的引物检测RNA呈阳性，而针对羧基末端15%的引物检测呈阴性。综合来看，我们的数据表明易位断点位于该基因的3'端。易位后的抗肌萎缩蛋白基因仍可表达为与质膜相关的截短型抗肌萎缩蛋白。我们的结果与易位导致更稳定的异常抗肌萎缩蛋白mRNA这一情况相符。
