Department of Medical Genetics and Genomic Medicine, School of Medicine, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, 13083-887, Brazil.
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
Cerebellum. 2019 Dec;18(6):1143-1146. doi: 10.1007/s12311-019-01055-z.
Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia in Caucasian populations. It is caused by a homozygous GAA expansion in the first intron of the frataxin gene (FXN) (OMIM: 606829) in 96% of the affected individuals. The remaining patients have a GAA expansion in one allele and a point mutation in the other. Little is known about compound heterozygous patients outside Europe and North America. We have thus designed a study to determine the frequency and mutational profile of these patients in Brazil. To accomplish that, we recruited all patients with ataxia and at least one expanded GAA allele at FXN from 3 national reference centers. We identified those subjects with a single expansion and proceeded with further genetic testing (Sanger sequencing and CGH arrays) for those. There were 143 unrelated patients (128 families), five of which had a single expanded allele. We identified point mutations in three out of these five (3/128 = 2.34%). Two patients had the c.157delC variant, whereas one individual had the novel variant c.482+1G>T. These results indicate that FXN point mutations are rare, but exist in Brazilian patients with FRDA. This has obvious implications for diagnostic testing and genetic counseling.
弗里德赖希共济失调（FRDA）是高加索人群中最常见的常染色体隐性共济失调。它是由 FXN 基因（OMIM：606829）第一个内含子中 GAA 扩增引起的，在 96%的受影响个体中为纯合子。其余患者在一个等位基因中有 GAA 扩增，另一个等位基因中有点突变。对于欧洲和北美的以外的复合杂合子患者，我们知之甚少。因此，我们设计了一项研究来确定巴西这些患者的频率和突变谱。为了实现这一目标，我们从 3 个国家参考中心招募了所有具有共济失调和至少一个 FXN 扩增 GAA 等位基因的患者。我们确定了那些具有单个扩增的受试者，并对这些受试者进行了进一步的遗传测试（Sanger 测序和 CGH 阵列）。共有 143 名无关患者（128 个家系），其中 5 名具有单个扩增等位基因。我们在这 5 名中的 3 名（3/128=2.34%）中发现了点突变。两名患者具有 c.157delC 变异，而一名患者具有新的 c.482+1G>T 变异。这些结果表明，FXN 点突变是罕见的，但存在于巴西 FRDA 患者中。这对诊断测试和遗传咨询具有明显的影响。
