Yoon G, Baskin B, Tarnopolsky M, Boycott K M, Geraghty M T, Sell E, Goobie S, Meschino W, Banwell B, Ray P N
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada,
Neurogenetics. 2013 Nov;14(3-4):181-8. doi: 10.1007/s10048-013-0366-9. Epub 2013 Jun 4.
We describe the clinical and genetic features of a well-characterized cohort of patients with autosomal recessive hereditary spastic paraplegia (ARHSP) in the province of Ontario. Patients with documented corticospinal tract abnormalities were screened by whole gene sequencing and multiplex ligation probe amplification for mutations in nine genes known to cause ARHSP. Of a cohort of 39 patients, a genetic diagnosis was established in 17 (44 %) and heterozygous mutations were detected in 8 (21 %). Mutations were most frequent in SPG7 (12 patients), followed by SPG11 (10 patients), PNPLA6 (SPG39, 2 patients), and ZFYVE26 (SPG15, 2 patients). Although there are associations between some clinical manifestations of ARHSP and specific genes, many patients are tested at an early stage of the disease when phenotype/genotype correlations are not obvious. Accurate molecular characterization of well-phenotyped cohorts of patients will be essential to establishing the natural history of these rare degenerative disorders to enable future clinical trials.
我们描述了安大略省一组特征明确的常染色体隐性遗传性痉挛性截瘫（ARHSP）患者的临床和遗传特征。对有记录的皮质脊髓束异常患者进行全基因测序和多重连接探针扩增，以检测已知会导致ARHSP的9个基因中的突变。在一组39例患者中，17例（44%）确诊了遗传诊断，8例（21%）检测到杂合突变。突变在SPG7中最为常见（12例患者），其次是SPG11（10例患者）、PNPLA6（SPG39，2例患者）和ZFYVE26（SPG15，2例患者）。虽然ARHSP的一些临床表现与特定基因之间存在关联，但许多患者在疾病早期进行检测时，表型/基因型的相关性并不明显。对表型良好的患者队列进行准确的分子特征分析对于确定这些罕见退行性疾病的自然史以开展未来的临床试验至关重要。
