J Clin Neurol.  2014 Jul;10(3):257-261. 10.3988/jcn.2014.10.3.257.

Mutation analysis of SPAST, ATL1, and REEP1 in Korean Patients with Hereditary Spastic Paraplegia

• Kim TH
• Lee JH
• Park YE
• Shin JH
• Nam TS
• Kim HS
• Jang HJ
• Semenov A
• Kim SJ
• Kim DS

• KMID: 2179454
• DOI: http://doi.org/10.3988/jcn.2014.10.3.257

Abstract

BACKGROUND AND PURPOSE
Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders that are characterized by progressive spasticity and weakness of the lower limbs. Mutations in the spastin gene (SPAST) are the most common causes of HSP, accounting for 40-67% of autosomal dominant HSP (AD-HSP) and 12-18% of sporadic cases. Mutations in the atlastin-1 gene (ATL1) and receptor expression-enhancing protein 1 gene (REEP1) are the second and third most common causes of AD-HSP, respectively.
METHODS
Direct sequence analysis was used to screen mutations in SPAST, ATL1, and REEP1 in 27 unrelated Korean patients with pure and complicated HSP. Multiplex ligation-dependent probe amplification was also performed to detect copy-number variations of the three genes.
RESULTS
Ten different SPAST mutations were identified in 11 probands, of which the following 6 were novel: c.760A>T, c.131C>A, c.1351_1353delAGA, c.376_377dupTA, c.1114A>G, and c.1372A>C. Most patients with SPAST mutations had AD-HSP (10/11, 91%), and the frequency of SPAST mutations accounted for 66.7% (10/15) of the AD-HSP patients. No significant correlation was found between the presence of the SPAST mutation and any of the various clinical parameters of pure HSP. No ATL1 and REEP1 mutations were detected.
CONCLUSIONS
We conclude that SPAST mutations are responsible for most Korean cases of genetically confirmed AD-HSP. Our observation of the absence of ATL1 and REEP1 mutations needs to be confirmed in larger series.

Keyword

hereditary spastic paraplegia; SPAST; ATL1; REEP1; Korea

MeSH Terms

Humans
Korea
Lower Extremity
Multiplex Polymerase Chain Reaction
Muscle Spasticity
Neurodegenerative Diseases
Sequence Analysis
Spastic Paraplegia, Hereditary*

Figure

• 

  Fig. 1 Organization of spastin and location of SPAST mutations identified in Korean HSP patients. *Nonsense mutations. AAA: ATPases Associated with a wide variety of Activities, HD: hydrophobic domain, HSP: hereditary spastic paraplegia, MIT: microtubule interacting and trafficking domain, MTBD: microtubule binding domain.

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