Brigatti Karlla W, Deutsch Eric C, Lynch David R, Farmer Jennifer M
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Child Neurol. 2012 Sep;27(9):1146-51. doi: 10.1177/0883073812448440. Epub 2012 Jun 29.
Friedreich ataxia is the most common inherited ataxia, with a wide phenotypic spectrum. It is generally caused by GAA expansions on both alleles of FXN, but a small percentage of patients are compound heterozygotes for a pathogenic expansion and a point mutation. Two recent diagnostic innovations are further characterizing individuals with the phenotype but without the classic genotypes. First, lateral-flow immunoassay is able to quantify the frataxin protein, thereby further characterizing these atypical individuals as likely affected or not affected, and providing some correlation to phenotype. It also holds promise as a biomarker for clinical trials in which the investigative agent increases frataxin. Second, gene dosage analysis and the identification of affected individuals with gene deletions introduce a novel genetic mechanism of disease. Both tests are now clinically available and suggest a new diagnostic paradigm for the disorder. Genetic counseling issues and future diagnostic testing approaches are considered as well.
弗里德赖希共济失调是最常见的遗传性共济失调，具有广泛的表型谱。它通常由FXN两个等位基因上的GAA重复扩增引起，但一小部分患者是致病性重复扩增和点突变的复合杂合子。最近的两项诊断创新正在进一步明确具有该表型但无经典基因型的个体。首先，侧向流动免疫测定能够定量法呢基化蛋白，从而进一步将这些非典型个体区分为可能患病或未患病，并与表型有一定关联。它还有望作为一种生物标志物用于研究药物可增加法呢基化蛋白的临床试验。其次，基因剂量分析以及对基因缺失的患病个体的识别引入了一种新的疾病遗传机制。这两种检测目前均可用于临床，为该疾病提出了一种新的诊断模式。还考虑了遗传咨询问题和未来的诊断检测方法。
