Meloni Mario, Farris Rita, Solla Paolo, Mascia Marcello M, Marrosu Francesco, Cannas Antonino
Department of Neurology, Institute of Neurology, Movement Disorders Center, University of Cagliari, Cagliari, Italy.
Neurologist. 2017 Nov;22(6):245-246. doi: 10.1097/NRL.0000000000000147.
Large expansions of the noncoding GGGGCC repeat (more than 30) in the first intron of the C9ORF72 gene have been demonstrated to cause amyotrophic lateral sclerosis and frontotemporal dementia. Recent papers have investigated the possible pathogenic role and associated clinical phenotypes of hexanucleotide expansions with intermediate repeat lengths ranging between 20 and 29 repeats.
We report a case of a 71-year-old Sardinian female patient with a long history of psychiatric disorders such as mixed anxiety-depressive disorder associated with somatization disorder and histrionic personality who developed a slowly progressive cerebellar syndrome, mild cognitive impairment, pyramidal signs, and rapid eye movement sleep behavior disorder with imaging abnormalities on the DaTSCAN single-photon emission computed tomography indicating an alteration in the presynaptic dopaminergic system. The patient was found to have intermediate C9ORF72 repeat expansions.
Early psychiatric presentations are a recurrent phenotypic manifestation of C9ORF72 expansions. In our patient, the intermediate C9ORF72 repeat expansion may have a pathogenic role in the cooccurrence of psychiatric and sleep disorders, cognitive dysfunctions, pyramidal system involvement, and late-onset cerebellar ataxia. This observation widens the spectrum of neurodegenerative conditions linked to C9ORF72 mutations.
已证实C9ORF72基因第一内含子中的非编码GGGGCC重复序列大量扩增（超过30次）会导致肌萎缩侧索硬化症和额颞叶痴呆。近期论文研究了重复长度在20至29次之间的中间型六核苷酸扩增的可能致病作用及相关临床表型。
我们报告一例71岁的撒丁岛女性患者，有长期精神疾病史，如伴有躯体化障碍和表演型人格的混合性焦虑抑郁障碍，该患者出现了缓慢进展的小脑综合征、轻度认知障碍、锥体束征和快速眼动睡眠行为障碍，DaTSCAN单光子发射计算机断层扫描显示影像学异常，提示突触前多巴胺能系统改变。该患者被发现存在中间型C9ORF72重复序列扩增。
早期精神症状是C9ORF72扩增反复出现的表型表现。在我们的患者中，中间型C9ORF72重复序列扩增可能在精神和睡眠障碍、认知功能障碍、锥体系统受累及迟发性小脑共济失调的共病中起致病作用。这一观察结果拓宽了与C9ORF72突变相关的神经退行性疾病谱。
