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Mutation Analysis of SPG4 and SPG3A Genes and Its Implication in Molecular Diagnosis of Korean Patients With Hereditary Spastic Paraplegia
Su-Yon Park, MD;
Chang-Seok Ki, MD, PhD;
Hee-Jin Kim, MD;
Jong-Won Kim, MD, PhD;
Duk Hyun Sung, MD, PhD;
Byoung Joon Kim, MD, PhD;
Won Yong Lee, MD, PhD
Arch Neurol. 2005;62:1118-1121.
Background Hereditary spastic paraplegia (HSP), a genetically and clinically heterogeneous group of neurodegenerative disorders, is characterized by progressive lower limb weakness and spasticity. Among the 8 loci associated with the autosomal dominant uncomplicated HSP (AD-HSP), the spastin (SPG4) and atlastin (SPG3A) genes have been known to account for approximately 40% and 10% of all cases, respectively.
Objective To investigate the contribution of these 2 genes in the occurrence of HSP in Korean patients.
Design Clinical and genetic study.
Setting Tertiary care center.
Patients Eighteen patients with uncomplicated HSP (11 AD and 7 sporadic) underwent screening for gene mutation.
Main Outcome Measures Mutations in the SPG4 and SPG3A genes as detected by direct sequencing of all coding exons and flanking intronic sequences.
Results We identified 8 different SPG4 mutations, 7 of which have not been reported elsewhere. Among the detected mutations were 3 missense mutations, 2 in-frame deletions, 2 frameshift mutations, and 1 splice-site mutation. No mutation was found in the SPG3A gene.
Conclusion Compared with previous studies, a higher frequency of SPG4 gene mutations in AD-HSP (7/11; 64%) was observed, suggesting that a mutation analysis for the SPG4 gene might be helpful for molecular diagnosis of AD-HSP in Korean patients.
Author Affiliations: Departments of Laboratory Medicine (Drs Park, Ki, H.-J. Kim, and J.-W. Kim), Physical Medicine and Rehabilitation (Dr Sung), and Neurology (Drs B. J. Kim and Lee), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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