Posted - June 2014 in Research Highlights
Six new mutations found
Six new SPG4 HSP mutations have been found, including 3 missense mutations, one insertion and two larger exon deletions.
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.
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.
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).
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.
SOURCE: Parkinsonism Relat Disord. 2014 May 2. pii: S1353-8020(14)00174-6. doi: 10.1016/j.parkreldis.2014.04.021. [Epub ahead of print] Copyright © 2014 Elsevier Ltd. All rights reserved. PMID: 24824479 [PubMed – as supplied by publisher]
Spastin mutation screening in Chinese patients with pure hereditary spastic paraplegia.
- 1Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
- 2Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- 3Department 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: [email protected]
- 4Department of Neurology and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: [email protected].