Department of Neurology, UCSF Memory and Aging Center, University of California - San Francisco, Campus Box 1207, San Francisco, CA 94143, USA.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, 630 W 168th St, P&S 16, New York, NY 10032, USA.
Alzheimers Res Ther. 2012 Jul 19;4(4):27. doi: 10.1186/alzrt130. eCollection 2012.
Frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) are related but distinct neurodegenerative diseases. The identification of a hexanucleotide repeat expansion in a noncoding region of the chromosome 9 open reading frame 72 (C9ORF72) gene as a common cause of FTD/ALS, familial FTD, and familial ALS marks the culmination of many years of investigation. This confirms the linkage of disease to chromosome 9 in large, multigenerational families with FTD and ALS, and it promotes deeper understanding of the diseases' shared molecular FTLD-TDP pathology. The discovery of the C9ORF72 repeat expansion has significant implications not only for familial FTD and ALS, but also for sporadic disease. Clinical and pathological correlates of the repeat expansion are being reported but remain to be refined, and a genetic test to detect the expansion has only recently become clinically available. Consequently, individuals and their families who are considering genetic testing for the C9ORF72 expansion should receive genetic counseling to discuss the risks, benefits, and limitations of testing. The following review aims to describe genetic counseling considerations for individuals at risk for a C9ORF72 repeat expansion.
额颞叶变性（FTD）和肌萎缩侧索硬化症（ALS）是相关但不同的神经退行性疾病。在染色体 9 开放阅读框 72（C9ORF72）基因的非编码区发现六核苷酸重复扩增是 FTD/ALS、家族性 FTD 和家族性 ALS 的常见原因，这标志着多年研究的高潮。这证实了疾病与染色体 9 的联系，在具有 FTD 和 ALS 的大型、多代家族中，这促进了对这些疾病共同的分子 FTLD-TDP 病理学的更深入理解。C9ORF72 重复扩增的发现不仅对家族性 FTD 和 ALS 具有重要意义，对散发性疾病也具有重要意义。重复扩增的临床和病理相关性正在被报道，但仍有待进一步完善，并且检测扩增的遗传测试最近才在临床上可用。因此，正在考虑对 C9ORF72 扩增进行基因检测的个体及其家属应接受遗传咨询，以讨论检测的风险、益处和局限性。以下综述旨在描述对 C9ORF72 重复扩增风险个体进行遗传咨询的注意事项。
