Mutation Analysis of Small Heat Shock Protein 27 Gene in Chinese CMT Patients

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Vol. 62 No. 8, August 2005 Arch Neurol. 2005;62:1201-1207.

http://archneur.ama-assn.org/cgi/content/abstract/62/8/1201?etoc

Mutation Analysis of the Small Heat Shock Protein 27 Gene in Chinese

Patients With Charcot-Marie-Tooth Disease

Beisha Tang, MD; Xiaomin Liu, MD; Guohua Zhao, MD, PhD; Wei Luo, MD,

PhD; Kun Xia, PhD; Qian Pan; Fang Cai, MD, PhD; Zhengmao Hu, PhD;

Cheng Zhang, MD, PhD; Biao Chen, MD, PhD; Fufeng Zhang, MD; Lu Shen,

MD, PhD; Ruxu Zhang, MD, PhD; Hong Jiang, MD, PhD

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.

Design 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.

Author Affiliations: Department of Neurology, Xiangya Hospital (Drs

Tang, Liu, Zhao, F. Zhang, Shen, R. Zhang, and Jiang), and National

Laboratory of Medical Genetics of China (Drs Tang, Xia, Cai, and Hu,

and Mr Pan), Central South University, Changsha; and Department of

Neurology, Qianfoshan Hospital, Jinan (Dr Liu) and Second Affiliated

Hospital, College of Medicine, Zhejiang University, Hangzhou (Dr

Luo), First Affiliated Hospital, Sun Yat-sen University, Guangzhou

(Dr C. Zhang), and Xuanwu Hospital, Capital University of Medical

Sciences, Beijing (Dr Chen), People's Republic of China.