PP99. NOVEL ETHNIC SPECIFIC MUTATIONS IN BULGARIAN PATIENTS WITH WILSON DISEASE
THEODOR TODOROV1, Aleksey Savov1, Violeta Mihaylova2, Zaharii Krustev3, Hristo Jelev4, Ivailo Tournev2, Veselin Penkov5, Dimitrina Konstantinova6, Ljudmila Tankova7, Nadejda Tzolova7 and Ivo Kremensky1. 1. Laboratory of Molecular Pathology, University Hospital of Obstetrics and Gynecology, Medical University, Sofia; 2. Department of Neurology, University Hospital "Alexandrovska", Sofia 3. Department of Gastroenterology, University Hospital "St. Ivan Rilski", Sofia 4. Department of Cell Biology Histology and Embryology, University "St. Kliment Ohridski", Sofia 5. Department of Pediatrics, Medical University, Sofia; 6. Department of Pediatrics and Medical Genetics, Medical University, Varna 7. Department of Gastroenterology, University Hospital "Queen Joanne", Sofia e-mail: theodor_todorov@hotmail.com
*Corresponding Author:
page: 91

Abstract

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.

 

Table 1.  Genotypes among the three ethnic groups in the Bulgarian population.

 

?

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

 

* Novel mutations detected in our study

** Other haplotypes associated with the mutation H1069Q: In Ethnic Bulgarians- 141/144; 141/148, 143/146; 143/144; 143/148, 143/150, 139/144; 147/146, 147/148,147/150; In Ethnic Roma (Gypsies)-141/144, 143/146, 139/144, 147/146.

 

 




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