Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease.
BACKGROUND
Charcot-Marie-Tooth (CMT) disease, the most common hereditary peripheral neuropathy, is highly clinically and genetically heterogeneous, and mutations in at least 18 genes have been identified. Recently, mutations in small heat shock protein 27 (Hsp27) were reported to cause CMT disease type 2F and distal hereditary motor neuropathy.


OBJECTIVE
To investigate the frequency and phenotypic features of an Hsp27 mutation in Chinese patients with CMT disease.


METHODS
DNA samples from 114 unrelated patients with CMT disease were screened for mutations in Hsp27 by polymerase chain reaction and direct sequencing. A cosegregated study was performed using the MbiI restriction endonuclease, and 50 healthy control subjects were analyzed. Haplotype analysis was performed using 5 short tandem repeat markers to analyze whether the families with the same mutation probably had a common ancestor.


RESULTS
One missense mutation, C379T, was detected in 4 autosomal dominant families with CMT disease type 2, and haplotype analysis indicated that the 4 families probably had a common founder. The frequency of the Hsp27 mutation is 0.9% (1/111) in Chinese patients with CMT disease in our study, and the phenotypes were characterized by later onset (age, 35-60 years) and mild sensory impairments. Electrophysiological findings showed moderately to severely slowed nerve conduction velocities in lower limb nerves but normal or mildly reduced velocities in upper limb nerves.


CONCLUSIONS
To our knowledge, this is the first report of an Hsp27 mutation in the People's Republic of China. The C379T mutation in Hsp27 also causes CMT disease type 2, except for distal hereditary motor neuropathy, and the phenotypes are distinct from the family with CMT disease type 2F described previously. A mutation of Hsp27 may be uncommon in Chinese patients with CMT disease.
Tang
Beisha
B
Department of Neurology, Xiangya Hospital, Central South University, Changsha, People's Republic of China. bstang7398@yahoo.com.cn
Liu
Xiaomin
X
Zhao
Guohua
G
Luo
Wei
W
Xia
Kun
K
Pan
Qian
Q
Cai
Fang
F
Hu
Zhengmao
Z
Zhang
Cheng
C
Chen
Biao
B
Zhang
Fufeng
F
Shen
Lu
L
Zhang
Ruxu
R
Jiang
Hong
H
D000328:Adult; D017668:Age of Onset; D002607:Charcot-Marie-Tooth Disease / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005820:Genetic Testing; D055551:HSP27 Heat-Shock Proteins; D006239:Haplotypes / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D020125:Mutation, Missense / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009431:Neural Conduction / Q000235:genetics; D010375:Pedigree; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins