Spastin mutation screening in Chinese patients with pure hereditary spastic paraplegia.
BACKGROUND
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative diseases. Mutations in the spastin (SPAST) gene are the most common cause of pure HSP. However, few data are available regarding the clinical and genetic spectrum of HSP among Chinese patients.


METHODS
Clinical data were collected at diagnosis and follow-up of 42 Chinese patients with pure HSP. All seventeen exons of the SPAST gene were directly sequenced. Additionally, we used a multiplex ligation dependent probe amplification (MLPA) assay targeting the SPAST gene to evaluate large exon deletion or insertion mutations in patients without SPAST point mutations.


RESULTS
The age of disease onset of our patients was 19.6 ± 14.4 years. Six novel variations were found, including three missense mutations (p. L363P, p. D441V, and p. S595R), one insertion (c.1511dupT (p. Y505Ifs*7)), and two larger deletions (exons 5-17 and exons 10-17). Four previously reported mutations, including p. S399L, c.1215_c.1219delTATAA (p. N405Kfs*36), exon 1 deletion, and exon 16 deletion, were detected. The SPAST mutation rate was 40% (4/10) in Chinese familial patients and 33.33% (7/21) in Chinese sporadic pure HSP patients. The frequency of large deletions was high in both AD-HSP (20%, 2/10) and sporadic HSP (14.28%, 3/21).


CONCLUSIONS
SPAST mutations are common in Chinese patients with pure HSP. Large exon deletions are an important cause of AD-HSP and sporadic pure HSP in Chinese patients. Large fragment tests should be performed to explore large SPAST mutations in familial and sporadic HSP patients without SPAST point mutations.
Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Qian-Qian
QQ
Wei
Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
YongPing
Y
Chen
Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Zhen-Zhen
ZZ
Zheng
Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
XuePing
X
Chen
Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Rui
R
Huang
Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yuan
Y
Yang
Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Department of Neurology, Bern University, Bern CH3010, Switzerland. Electronic address: jean-marc.burgunder@dkf.unibe.ch.
JeanMarc
J
Burgunder
Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: hfshang2002@126.com.
Hui-Fang
HF
Shang
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human
Hereditary spastic paraplegia; MLPA; Mutation; SPAST