A novel insertion mutation in spastin gene is the cause of spastic paraplegia in a Chinese family.
A total of eight loci for autosomal dominant hereditary spastic paraplegia (ADHSP) has been mapped to chromosome 14q, 2p, 15q, 8q, 10q, 12q, 19q, 2q, respectively, among which the SPG4 gene on chromosome 2p21-22 encoding spastin, an ATPase of the AAA family, accounts for 40-50% of all ADHSP families and is expressed in both adult and fetal tissues. In this work, we reveal a novel insertion mutation in exon 11 of the SPG4 gene found in a big Chinese family composed of 47 members, including 20 affected ones, using linkage analysis. The mutation was well demonstrated to be the cause of loss of production of the functional protein by pre-termination of translation in AAA cassette region. To our knowledge, this is the first report of spastin mutation in China.
Shanghai Research Center of Life Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China.
Wei
W
Qin
Tao
T
Zhang
Ju
J
Han
LiQun
L
Tang
XingWang
X
Li
GuoYin
G
Feng
WanQing
W
Liu
Lin
L
He
D000251:Adenosine Triphosphatases; D044466:Asian People / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010641:Phenotype; D015183:Restriction Mapping; D015419:Spastic Paraplegia, Hereditary / Q000209:etiology / Q000235:genetics*; D000074181:Spastin
D002135:Calcium-Binding Proteins; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human