Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière (ICM), AP-HP - Hôpital Pitié-Salpêtrière, Paris, France; Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France.
UF de Neurogénétique Moléculaire et Cellulaire, Département de Génétique, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France.
Neurobiol Aging. 2018 Dec;72:187.e11-187.e14. doi: 10.1016/j.neurobiolaging.2018.06.037. Epub 2018 Jun 30.
Valosin-containing protein (VCP) mutations are rare causes of autosomal dominant frontotemporal dementias associated with Paget's disease of bone, inclusion body myopathy, and amyotrophic lateral sclerosis. We analyzed the VCP gene in a cohort of 199 patients with frontotemporal dementia and identified 7 heterozygous mutations in unrelated families, including 3 novel mutations segregating with dementia. This expands the VCP mutation spectrum and suggests that although VCP mutations are rare (3.5% in this study), the gene should be analyzed even in absence of the full syndromic complex. Reporting genetic variants with convincing arguments for pathogenicity is important considering the large amount of data generated by next-generation sequencing and the growing difficulties to interpret rare genetic variants identified in isolated cases.
包涵体肌病伴运动神经元病和额颞叶痴呆的遗传性发病的 VCP 基因突变：罕见病因
VCP 基因突变是伴有 Pagets 骨病、包涵体肌病和肌萎缩性侧索硬化的常染色体显性额颞叶痴呆的罕见病因。我们在一组 199 例额颞叶痴呆患者中分析了 VCP 基因，在无关的家族中发现了 7 个杂合突变，包括 3 个与痴呆症分离的新突变。这扩大了 VCP 突变谱，并表明尽管 VCP 突变罕见（本研究中为 3.5%），但即使在没有完整的综合征性复杂情况下，也应分析该基因。考虑到下一代测序产生的大量数据以及在孤立病例中鉴定到的罕见遗传变异的解释越来越困难，报告具有致病性说服力的遗传变异非常重要。
