Wibawa T, Takeshima Y, Mitsuyoshi I, Wada H, Surono A, Nakamura H, Matsuo M
Division of Genetics, International Center for Medical Research, Kobe University School of Medicine, Kobe, Japan.
Brain Dev. 2000 Mar;22(2):107-12. doi: 10.1016/s0387-7604(99)00126-6.
Severe mental retardation is a rare complication of Duchenne muscular dystrophy (DMD). Here we report that two DMD cases showing severe mental retardation exhibit the same exon skipping event induced by different intron mutations. In the two Japanese DMD patients studied, the complete sequence of exon 66 of the dystrophin gene was found to be absent from the dystrophin mRNA, creating a premature stop codon in exon 67. Novel point mutations at the consensus sequence of the splice donor site of intron 66 (T9857(+2) to C in one case and G9857(+5) to T in the other case) were found to be the cause of complete exon skipping. Remarkably, severe mental retardation cosegregated with an exon 66-skipping event in their families. Furthermore, pachygyria was disclosed by magnetic resonance imaging (MRI) examination of the brain of one case. Our results suggested that exon 66 skipping should be examined in DMD cases with a severe form of mental retardation.
重度智力障碍是杜氏肌营养不良症（DMD）的一种罕见并发症。在此我们报告，两例表现出重度智力障碍的DMD病例出现了由不同内含子突变导致的相同外显子跳跃事件。在所研究的两名日本DMD患者中，发现肌营养不良蛋白基因外显子66的完整序列在肌营养不良蛋白mRNA中缺失，从而在外显子67中产生了一个提前终止密码子。发现在内含子66剪接供体位点的共有序列处存在新的点突变（一例为T9857(+2)突变为C，另一例为G9857(+5)突变为T）是导致外显子66完全跳跃的原因。值得注意的是，在他们的家族中，重度智力障碍与外显子66跳跃事件共分离。此外，对其中一例患者的脑部进行磁共振成像（MRI）检查发现了脑回增厚。我们的结果表明，对于患有重度智力障碍的DMD病例，应检查外显子66跳跃情况。
