Role of genotyping in Wilson’s disease

Schmidt, Hartmut

doi:10.1016/j.jhep.2008.11.008

Cited by 35 publications

(18 citation statements)

References 49 publications

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“…In the century since Wilson's original description of a universally fatal familial disease of the young, we have learned much about the disorder . We now recognize that the disease results from chronic copper toxicity in (primarily) the liver and brain and have identified the responsible gene . Though the search for a simple and reliable diagnostic test is ongoing, genetic analysis may soon provide a practical diagnostic screening tool .…”

Section: Resultsmentioning

confidence: 99%

“…WD is caused by homozygous or compound heterozygous mutation(s) in the ATP7B gene, and genetic analysis is the confirmatory test for the disease. However, until recently, mutational analysis remained an impractical diagnostic tool because there are over 600 mutations described and new ones continue to be reported . In the last few years, development of rapid whole‐gene sequencing has made it possible to reliably identify ATP7B mutations in over 98% of patients examined ,…”

Section: Recognizing Wdmentioning

confidence: 99%

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The Pragmatic Treatment of Wilson's Disease

Aggarwal

Bhatt

2014

Mov Disord Clin Pract

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Wilson's disease (WD) is a potentially fatal disorder of chronic copper toxicity, primarily affecting the liver and the brain. Judicious treatment can restore health and longevity, even in patients with severe neurological impairment. However, the disease is associated with considerable morbidity and mortality resulting from delay in diagnosis, and difficulty in pacing the medical treatment. In this article, we briefly review the diagnosis and treatment options for WD and share our experience in managing patients with WD. We focus on decoppering (copper chelation) treatment of WD and outline pragmatic strategies for patient management designed to recognize and minimize adverse effects while ensuring treatment compliance and effectiveness.

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Section: Resultsmentioning

confidence: 99%

Section: Recognizing Wdmentioning

confidence: 99%

The Pragmatic Treatment of Wilson's Disease

Aggarwal

Bhatt

2014

Mov Disord Clin Pract

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“…Interestingly, age at diagnosis, but not genotype, was correlated with urinary copper concentration. This information may account, in part, for the difficulty of WND diagnosis in children [47,48]. …”

Section: Discussionmentioning

confidence: 99%

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

Ling

et al. 2011

BMC Med Genet

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BackgroundWilson'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.MethodsThe 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).ResultsNeurologic 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).ConclusionsWe 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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“…The disease incidence is estimated to be 1 in 30,000 to 1 in in 50,000 3,4 , and it is supposed that the prevalence is 30 per million, with the frequency of heterozygotous mutations carriers of about 1 in 90 to 1 in 150 5,6 . Until now, it has been identified more than 400 mutations in ATP7B gene with characteristic geographic distribution 7,8 . In a study on Serbian population, molecular gene defect was identified in 80% of alleles of Wilson's disease patients, with 11 different mutations, and the most frequent mutations were H1069Q (48.9% of analyzed alleles), 2304-2305insC (11.4%), and A1003T (5.7%) 9 .…”

Section: Introductionmentioning

confidence: 99%