Affiliations: [a] Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| [b] Department of Psychiatry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| [c] Department of Neurology, Shanghai Putuo District People’s Hospital, Shanghai, China
| [d] Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
| [e] MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
Correspondence:
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Correspondence to: Dr. Ru-Jing Ren, Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. E-mail: doctorren2001@126.com and Dr. Zhao Qian-Hua, Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China. E-mail: qianhuazhao@fudan.edu.cn.
Note: [1] These authors contributed equally to this work.
Abstract: Background:Recently, Sigma nonopioid intracellular receptor 1 (SIGMAR1) variants have been shown harboring C9orf72 pathogenic repeat expansions in some frontotemporal dementia (FTD) cases. However, no SIGMAR1 genotype analysis has been reported in a cohort absent of C9orf72 pathogenic repeat expansions to date. Objective:The present study investigated the contribution of SIGMAR1 independent of C9orf72 gene status to FTD spectrum syndromes. Methods:We directly sequencing the entire coding region and a minimum of 50 bp from each of the flanking introns of SIGMAR1 gene in 82 sporadic FTD patients (female: male = 42 : 40) and 417 controls. For the patient carrying SIGMAR1 variant, a follow-up 3T MR imaging was performed in the study. Results:Gene sequencing of SIGMAR1 revealed a rare 3′UTR nucleotide variation rs192856872 in a male patient with semantic dementia independent of C9orf72 gene status. The MR imaging showed asymmetrical atrophy in the anterior temporal lobes and the degeneration extends caudally into the posterior temporal lobes as the disease progresses. ESEFinder analysis showed new SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores, which is predicted to affect normal splicing. Conclusion:We found a novel SIGMAR1 variant independent of C9orf72 gene status associated with semantic dementia phenotype.
