Tassone F, Hagerman R J, Taylor A K, Mills J B, Harris S W, Gane L W, Hagerman P J
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Am J Med Genet. 2000 Mar 13;91(2):144-52. doi: 10.1002/(sici)1096-8628(20000313)91:2<144::aid-ajmg14>3.0.co;2-v.
Most individuals with the fragile X premutation are clinically unaffected; however, some show clinical manifestations, including learning difficulties, emotional problems, or even mental retardation. The basis of clinical involvement in these individuals is unknown. Premutation alleles are reportedly associated with normal levels of mRNA and protein (FMRP). To examine this issue in more detail, we studied six individuals with a premutation. We are reporting these cases to demonstrate a spectrum of phenotypic involvement which can be seen clinically. These cases include one individual with the premutation who has no evidence of FMR1 gene dysfunction but has mental retardation from other causes. Other cases presented here show varying degrees of FMR1 gene dysfunction as assessed by FMRP and FMR1 mRNA levels and various clinical features of fragile X. In two cases we observed a significant reduction in FMRP expression and an elevated FMR1 mRNA expression level associated with moderate cognitive deficit. Thus, the utilization of FMRP measures can be helpful in understanding for which premutation patients clinical involvement is caused by dysfunction of the FMR1 gene.
大多数具有脆性X前突变的个体在临床上并无异常；然而，一些个体表现出临床表现，包括学习困难、情绪问题，甚至智力迟钝。这些个体出现临床症状的原因尚不清楚。据报道，前突变等位基因与正常水平的mRNA和蛋白质（FMRP）相关。为了更详细地研究这个问题，我们研究了6名具有前突变的个体。我们报告这些病例以展示临床上可见的一系列表型表现。这些病例包括一名具有前突变但无FMR1基因功能障碍证据但因其他原因导致智力迟钝的个体。此处呈现的其他病例显示，根据FMRP和FMR1 mRNA水平以及脆性X的各种临床特征评估，FMR1基因功能存在不同程度的障碍。在两例病例中，我们观察到FMRP表达显著降低，FMR1 mRNA表达水平升高，同时伴有中度认知缺陷。因此，利用FMRP检测有助于理解哪些前突变患者的临床症状是由FMR1基因功能障碍引起的。
