A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia.
Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities. Among eight loci linked with autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about 40% of all patients. Recently, mutations in a new member of the AAA protein family, called spastin, have been identified as responsible for SPG4-linked AD-HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of the SPG4 gene identified in a Korean family with typical clinical features of pure AD-HSP. The mutation affects the third amino acid of the highly conserved AAA cassette domain, which is the most fore part of the domain altered by a missense mutation reported so far. Clinical presentations of affected individuals carrying the I344K mutation were not different from those of pure AD-HSP with SPG4 mutations reported previously. However, it is noteworthy that neither urinary dysfunction nor involvement of upper extremities was noticed in this family. To our knowledge, this is the first report of genetically confirmed AD-HSP in Korea.
Department of Clinical Pathology, Sungkyunkwan University School of Medicine, Samsung Medical Center, #50 Ilwon-Dong, Kangnam-Gu, Seoul 135-710, Korea.
Chang-Seok
CS
Ki
Won Yong
WY
Lee
Do Hoon
DH
Han
Duk Hyun
DH
Sung
Kyung-Bok
KB
Lee
Kyung-A
KA
Lee
Sang Seon
SS
Cho
Seunghee
S
Cho
Hyokkee
H
Hwang
Kwang Min
KM
Sohn
Yeun Joo
YJ
Choi
Jong-Won
JW
Kim
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010264:Paraplegia / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D000074181:Spastin
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human