Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations

• Main Authors: De-Min Yu (Author), Zhou Feng (Author), Zang Guo-Qing (Author), Xu Jie (Author), Fu Qing-Chun (Author), Ling Yun (Author), Lu Yi (Author), Li Xin-Hua (Author), Han Yue (Author), Zhang Dong-Hua (Author), Gong Qi-Ming (Author), Lu Zhi-Meng (Author), Kong Xiao-Fei (Author), Wang Jian-She (Author), Zhang Xin-Xin (Author)
• Format: Book
• Published: BMC, 2011-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>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 <it>ATP7B </it>mutations and to more completely characterize WND in China.</p> <p>Methods</p> <p>The coding and promoter regions of the <it>ATP7B </it>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).</p> <p>Results</p> <p>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).</p> <p>Conclusions</p> <p>We identified 14 novel mutations and found that the spectrum of mutations of <it>ATP7B </it>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.</p>

Item Description

10.1186/1471-2350-12-6
1471-2350