Mutation analysis of SPG4 and SPG3A genes and its implication in molecular diagnosis of Korean patients with hereditary spastic paraplegia.
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.


METHODS
Clinical and genetic study.


METHODS
Tertiary care center.


METHODS
Eighteen patients with uncomplicated HSP (11 AD and 7 sporadic) underwent screening for gene mutation.


METHODS
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.


CONCLUSIONS
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.
Park
Su-Yon
SY
Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ki
Chang-Seok
CS
Kim
Hee-Jin
HJ
Kim
Jong-Won
JW
Sung
Duk Hyun
DH
Kim
Byoung Joon
BJ
Lee
Won Yong
WY
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007723:Korea; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015419:Spastic Paraplegia, Hereditary / Q000208:ethnology / Q000235:genetics*; D000074181:Spastin
D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human