TY - JOUR
T1 - Clinical and molecular characterization of Wilson's disease in China
T2 - Identification of 14 novel mutations
AU - Li, Xin Hua
AU - Lu, Yi
AU - Ling, Yun
AU - Fu, Qing Chun
AU - Xu, Jie
AU - Zang, Guo Qing
AU - Zhou, Feng
AU - De-Min, Yu
AU - Han, Yue
AU - Zhang, Dong Hua
AU - Gong, Qi Ming
AU - Lu, Zhi Meng
AU - Kong, Xiao Fei
AU - Wang, Jian She
AU - Zhang, Xin Xin
N1 - Funding Information:
This project was supported by National Natural Science Foundation of China (No. 30800612), Shanghai Educational Development Foundation (X.F, Kong 2007CG20) and National Special Key Grant (2008ZX10002 - 007). We also thank Prof. Nelly Kieffer (CNRS-UMR7151, Sino-French Research Center for Life Sciences and Genomics, Shanghai, China) for helpful discussions and revising the English of the manuscript.
PY - 2011/1/11
Y1 - 2011/1/11
N2 - Background: Wilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of ATP7B mutations and to more completely characterize WND in China.Methods: The coding and promoter regions of the ATP7B gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 ~ 61 years old).Results: Neurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p.Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p.Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065).Conclusions: We identified 14 novel mutations and found that the spectrum of mutations of ATP7B in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.
AB - Background: Wilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of ATP7B mutations and to more completely characterize WND in China.Methods: The coding and promoter regions of the ATP7B gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 ~ 61 years old).Results: Neurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p.Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p.Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065).Conclusions: We identified 14 novel mutations and found that the spectrum of mutations of ATP7B in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.
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U2 - 10.1186/1471-2350-12-6
DO - 10.1186/1471-2350-12-6
M3 - Article
C2 - 21219664
AN - SCOPUS:78651074120
SN - 1471-2350
VL - 12
JO - BMC Medical Genetics
JF - BMC Medical Genetics
M1 - 6
ER -