J Genet Med.  2011 Jun;8(1):53-57. 10.5734/JGM.2011.8.1.53.

Association of a c.1084A>G (p.Thr362Ala)Variant in the DCTN4 Gene with Wilson Disease

• Lee DW
• Kim JJ
• Kim JH
• Lee JK
• Yoo HW

• KMID: 1851091
• DOI: http://doi.org/10.5734/JGM.2011.8.1.53

Abstract

PURPOSE
Wilson disease is an autosomal recessive disorder which causes excessive copper accumulation in the hepatic region. So far, ATP7B gene is the only disease-causing gene of Wilson disease known to date. However, ATP7B mutations have not been found in ~15% of the patients. This study was performed to identify any causative gene in Wilson disease patients without an ATP7B mutation in either allele.
MATERIALS AND METHODS
The sequence of the coding regions and exon-intron boundaries of the five ATP7B-interacting genes, ATOX1, COMMD1, GLRX, DCTN4, and ZBTB16, were analyzed in the 12 patients with Wilson disease.
RESULTS
Three nonsynonymous variants including c.1084A>G (p.Thr362Ala) in the exon 12 of the DCTN4 gene were identified in the patients examined. Among these, only p.Thr362Ala was predicted as possibly damaging protein function by in silico analysis. Examination of allele frequency of c.1084A>G (p.Thr362Ala) variant in the 176 patients with Wilson disease and in the 414 normal subjects revealed that the variant was more prevalent in the Wilson disease patients (odds ratio [OR]=3.14, 95% confidence interval=1.36-7.22, P=0.0094).
CONCLUSION
Our result suggests that c.1084A>G (p.Thr362Ala) in the ATP7B-interacting DCTN4 gene may be associated with the pathogenesis of Wilson disease.

Keyword

Wilson disease; DCTN4; ATP7B-interacting genes; Polymorphism; Association

MeSH Terms

Clinical Coding
Computer Simulation
Copper
Exons
Gene Frequency
Hepatolenticular Degeneration
Humans
Copper