Clinical features of Chinese patients with Gerstmann-Sträussler-Scheinker identified by targeted next-generation sequencing.
Gerstmann-Sträussler-Scheinker (GSS) is an autosomal dominant neurodegenerative disease due to mutations within prion protein (PRNP) gene. Clinically, it is not easy to distinguish GSS from spinocerebellar ataxia (SCA), especially in the early stage of disease. We aimed to identify genetic mutations in 8 Chinese pedigrees with dominant ataxia but excluded dynamic mutations of SCA genes. Targeted next-generation sequencing was performed in the 8 probands. A customized panel was designed to capture 24 known causative genes, including 15 autosomal dominant SCA genes and 9 dementia-related genes. A 2-year follow-up was performed in these patients who harbored mutation. Of the 8 probands, 5 were identified to harbor the p.P102L mutation within PRNP. All these 5 cases had progressive ataxia with age at onset ranging from 48 to 52 years (49.5 ± 4.51). Remarkable phenotypic heterogeneity was observed in them. Cognitive decline was found in 4/5 probands. The average duration from initial symptoms to cognitive decline is 32.5 months, ranging from 22 to 48 months. In this study, we presented the detailed clinical features of 5 GSS pedigrees with PRNP p.P102L mutation. The variable phenotypes among these GSS patients indicated other genetic or environmental factors might be involved in the phenotypic heterogeneity of GSS. Our findings also support the proposal that screening of PRNP mutations should be performed for the patients with dominant ataxia if dynamic mutations of SCA genes were excluded.
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Hong-Fu
HF
Li
Department of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
Zhi-Jun
ZJ
Liu
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Hai-Lin
HL
Dong
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Juan-Juan
JJ
Xie
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Shao-Yun
SY
Zhao
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Wang
W
Ni
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
Yi
Y
Dong
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: zhiyingwu@zju.edu.cn.
Zhi-Ying
ZY
Wu
D000328:Adult; D044466:Asian People / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D056726:Genetic Association Studies; D016098:Gerstmann-Straussler-Scheinker Disease / Q000175:diagnosis / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D000072002:Prion Proteins / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics
C512656:PRNP protein, human; D000072002:Prion Proteins
Gerstmann–Sträussler–Scheinker; PRNP; Prion diseases; Targeted next-generation sequencing