一个家族性肌萎缩侧索硬化症家系，该家系中存在一个新型的 OPTN 杂合子 p.Glu46Asp 变异和 SOD1 错义突变 p.Ala5Val 的杂合子，这两种变异在该家系中表现不一致。
A familial amyotrophic lateral sclerosis pedigree discordant for a novel p.Glu46Asp heterozygous OPTN variant and the p.Ala5Val heterozygous SOD1 missense mutation.
机构信息
ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza, SC Neurologia 1U, Turin, Italy.
ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy.
出版信息
J Clin Neurosci. 2020 May;75:223-225. doi: 10.1016/j.jocn.2020.03.032. Epub 2020 Mar 27.
About 10% of Amyotrophic Lateral Sclerosis (ALS) cases are familial (FALS), mainly related to mutations in C9ORF72, SOD1, TARDBP, and FUS genes. Recent data revealed the presence of multiple variants in ALS-associated genes in FALS in excess of what is to be expected by chance. FALS patients not carrying a pathogenic genetic mutation detected in their kindred have been reported. We report a FALS case, who did not carry the p.Ala5Val heterozygous SOD1 mutation that had been detected in other affected subjects of his kindred. He underwent Next-Generation Sequencing, revealing a novel p.Glu46Asp heterozygous OPTN variant of uncertain significance (VUS). Discordant genetic test results in FALS cases within the same family and the detection of variants of uncertain significance increase the complexities of genetic counselling.
约 10%的肌萎缩侧索硬化症（ALS）病例为家族性（FALS），主要与 C9ORF72、SOD1、TARDBP 和 FUS 基因突变有关。最近的数据显示，FALS 患者的 ALS 相关基因中存在多种变异，超出了预期的随机变异。据报道，一些 FALS 患者的家族中并未检测到致病性基因突变。我们报告了一个 FALS 病例，他没有携带其家族中其他受累个体检测到的 SOD1 突变 p.Ala5Val 杂合子。他进行了下一代测序，发现了一个新的 OPTN 变异 p.Glu46Asp 杂合子，意义不明（VUS）。同一家庭内 FALS 病例的遗传检测结果不一致，以及意义不明的变异的检测增加了遗传咨询的复杂性。
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