Objective: Genetic analysis of Taiwanese patients with Wilson’s disease.

Background: Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism. The genetic cause is ATP7B mutations which lead to an accumulation of copper in body, particularly in the liver, brain, cornea, and skeletal system. The patients typically present with hepatic or neurological symptoms but the phenotype varies greatly even in the same family. The disease most commonly occurs in childhood and young adulthood, and is progressive and fatal if left untreated.

Methods: The genetic analysis was conducted by using Sanger sequencing for coding region of ATP7B gene and multiple-ligation probe amplification (MLPA) for exonic deletion.

Results: The ATP7B mutations were detected in 79 of 83 WD patients (male/female, 50/33). The mean onset age was 19. 6±7.6 years and time of onset to diagnosis delayed more than one year in 14 patients. The serum ceruloplasmin and copper were 4.79±2.78 mg/dL and 28.28±21.06 ug/dL, respectively. In 60 patients with neurological manifestations, the most common symptom was tremor (60%), followed by dystonia (37%), parkinsonism (15%), and seizure (10%). The p.Arg778Leu (24.7%) is the most common mutation, followed by p.Pro992Leu (17.5%), p.Gly943Asp (7.8%), p.Ile1148Thr (6.6%), p.Met1169Leu (6.6%), and Thr935Met (6%). The prevalent exons were exon 8, 12, 13, 16, and 18, accounting for two third of cases. There was one family with exon10/11 deletion.

Conclusions: The genetic spectrum of WD in Taiwan is different from Western countries. The genetic testing for ATP7B mutations is helpful for the early diagnosis of Wilson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-analysis-of-wilsons-disease-in-taiwan/