Department of Neurological Sciences, University Federico II, Via Pansini 5, 80131 Naples, NA, Italy.
J Neurol. 2013 Apr;260(4):1116-21. doi: 10.1007/s00415-012-6770-5. Epub 2012 Nov 30.
Friedreich ataxia (FRDA) is caused by a GAA expansion in the first intron of the FXN gene, which encodes frataxin. Four percent of patients harbor a point mutation on one allele and a GAA expansion on the other. We studied an Italian patient presenting with symptoms suggestive of FRDA, and carrying a single expanded 850 GAA allele. As a second diagnostic step, frataxin was measured in peripheral blood mononuclear cells, and proved to be in the pathological range (2.95 pg/μg total protein, 12.7 % of control levels). Subsequent sequencing revealed a novel deletion in exon 5a (c.572delC) which predicted a frameshift at codon 191 and a premature truncation of the protein at codon 194 (p.T191IfsX194). FXN/mRNA expression was reduced to 69.2 % of control levels. Clinical phenotype was atypical with absent dysarthria, and rapid disease progression. L-Buthionine-sulphoximine treatment of the proband's lymphoblasts showed a severe phenotype as compared to classic FRDA.
弗里德赖希共济失调（FRDA）是由 FXN 基因第一内含子中的 GAA 扩展引起的，该基因编码 frataxin。4%的患者在一个等位基因上携带点突变，在另一个等位基因上携带 GAA 扩展。我们研究了一位意大利患者，其表现出 FRDA 的症状，并且携带单个扩展的 850 GAA 等位基因。作为第二个诊断步骤，在周围血单核细胞中测量了 frataxin，结果证明处于病理范围（2.95 pg/μg 总蛋白，为对照水平的 12.7%）。随后的测序揭示了外显子 5a 中的一个新缺失（c.572delC），预测在密码子 191 处发生移码，并导致蛋白在密码子 194 处过早截断（p.T191IfsX194）。FXN/mRNA 的表达降低至对照水平的 69.2%。临床表型不典型，无构音障碍，且疾病进展迅速。与经典 FRDA 相比，在用 L-丁硫氨酸亚砜胺处理先证者的淋巴母细胞时，观察到严重的表型。
