The same haplotype for two unrelated Wilson disease patients with new ATP7B mutation

Wilson disease is a rare autosomal recessive disorder of copper metabolism caused by mutation in the ATP7B gene. The combination of markers (such as SNPs) on a single chromosome can be used to understand the structure of haplotype in the human genome, in which provide notable information on the origin of the mutation in human genetic disorders. The purpose of this study was to determine a haplotype analysis of two unrelated Wilson disease patients with the same missense mutation, c.2335T>G (g.58164 T>G) in exon 8.

DNA was prepared from two patients with the c.2335T>G mutation, their first-degree relatives, and 50 selected homozygous individuals from consanguineous marriage for eight SNPs around this particular ATP7B mutation. PCR was performed for SNPs of exons 4 (g.47964 C>T), 5 (g.51482G>A), 6 (g.54622A>G), 7 (g.56255G>A), 9 (g.59042G>T), 11 (g.66363G>A), 13 (g.70004 G>C), and 14 (g.72244 A>G), which are located in upstream and downstream of this mutation. Then, restriction fragment length polymorphism (RFLP) for these eight SNPs was designed and performed using eight different restriction enzymes.

Eight different haplotypes were found in the present study and the patients with the same missense mutation had the same haplotype. The most prevalent haplotype in 100 normal studied ATP7B alleles was the same as reference haplotype (C G A G T G G G A) for ATP7B gene (NG_008806.1).

As these two geographically separated families with the same mutation had the same haplotype, we concluded that this mutation possibly had the same origin in this population.