Wilson disease is an autosomal recessive disorder caused by a defect in a metal transporting P-type ATPase, resulting in toxic copper accumulation in various tissues and cells with prevalence of 1:30 000. Mutation in ATP7B gene lead to a wide range of clinical symptoms including hepatic, neurological, or psychiatric presentations.

The present study describes a detailed mutation profile of Wilson disease in the three major ethnic groups in the Bulgarian population. We characterized the mutation in 96% of the WD chromosomes and identified 26 different mutations. Genetic differences were observed among the three ethnic groups in Bulgaria (Table 1).

An examination of associated with WD chromosomes haplotypes for the markers D13S314/D13S316 revealed 20 different combinations (Table 1). In the Roma WD chromosomes, the H1069Q mutation was preferentially associated with the most common haplotype (86.5%). It was spread on 4 different haplotypes and all of them present together with H1069Q in the Bulgarian sub sample too. A possible explanation of this finding could be that, H1069Q in the Roma population has been imported by admixture and has expanded with population growth. The same is valid for H1069Q associated with frequent haplotype, which we found in all patients with Turkish ethnic origin, homozygous for H1069Q, since this mutation is relative rare in Turkey, where the pattern of common mutations is different.

?	Mutation		Ethnic Bulgarians		Ethnic Turks		Ethnic Roma		Total
	aa	nt	Haplotype	Mut%	Haplotype	Mut%	Haplotype	Mut%	Alleles	Mut%
1	H1069Q	3207 C>A	141/146**	48,3	141/146	37,5	141/146**	96,2	139	57.91
2	P767P fs	2298-2299insC	141/148	10.47	141/148	12.5			20	8.40
3	R616Q	1847 G>A	147/148	6.40					11	4.62
4	P1134P fs	3400delC	147/150	4.65					8	3.36
5	G1341D	4022 G>A	143/150	4.07					7	2.94
6	V12171218L	3649-3654del 6	141/144	2.91					5	2.10
7	-	IVS4 -1: G>A	143/146	2.33			143/146	1.92	4	1.68
8	A874V	2621 C>T	141/144	2.33	141/144	28.6			6	2.52
9	R969Q	2906 G>A	143/150	2.33					4	1.68
10	A1003T	3007 G>A	141/146	2.33					4	1.68
11	K844K fs	2530 delA	151/144	1.74					3	1.25
12	R778G	2332 C>G	141/144	1.16					2	0.84
13	N505X	1512-1513insT			139/146	28.6			2	0.84
14	S71S fs	213_214delAT	No data	0.58					1	0.42
15	L282P fs	845 del T	141/142	0.58					1	0.42
16	-	IVS5-2A>G					139/142	1.92	1	0.42
17	G626A	1877 G>C	No data	0.58					1	0.42
18	R778W*	2332 C>T	141/142	0.58					1	0.42
19	L936X	2807 T>A	No data	0.58					1	0.42
20	I1236T	3707 T>C			No data	14.3			1	0.42
21	N1270S	3809 A>G	No data	0.58					1	0.42
22	N1270T*	3809 A>C	139/150	0.58					1	0.42
23	Q1277X*	3829 C>T			139/146	14.3			1	0.42
24	D1279Y	3835 G>T	143/150	0.58					1	0.42
25	P1352S	4054 C>T	149/150	0.58					1	0.42
26	L1368P	4103 T>C	149/150	0.58					1	0.42
	Unknown		8	4.65	1	14.3	-	-	9	3.75
	Total alleles		172	100.0	16	100.0	52	100.0	240	100