The His1069Gln mutation in the ATP7B gene in Romanian patients with Wilson's disease referred to a tertiary gastroenterology center.
OBJECTIVE
Wilson's disease (WD) is a rare autosomal recessive disease. More than 500 mutations have been described so far, out of which 29 in exon 14. H1069Q mutation in the exon 14 of ATP7B gene is the most frequently encountered in Europe. The aim of the present study was to evaluate the incidence of mutations occurring in exon 14 of ATP7B gene in Romanian patients referred to a tertiary gastroenterology center, with known or suspected WD and in asymptomatic first degree relatives of index cases.


METHODS
93 patients were included in the study. Exon 14 of ATP7B gene has been amplified by PCR from genomic DNA and mutations identified by sequencing.


RESULTS
Only H1069Q missense mutation was detected in our study group. In patients with an established diagnosis of WD (38 cases), 34.2% were heterozygous for H1069Q and 21.1% were homozygous, with an allelic frequency of 38.1%. In paediatric WD patients (12 cases) 25% were heterozygous and 16.7% were homozygous (not significant versus adult population). Among asymptomatic first degree relatives of patients with WD (12 siblings, 25 parents) there were 40.5% cases heterozygous for H1069Q. In patients with suspected WD (17 cases), only 5.9% were heterozygous and no homozygous patient was identified. In our study group, H1069Q screening alone could not raise the Leipzig score to confirm diagnosis in patients with suspected WD or in asymptomatic first degree relatives.


CONCLUSIONS
H1069Q mutation is highly prevalent in Romanian WD patients and first degree relatives, similar to other central and continental western European populations.
Gastroenterology and Hepatology Center, Fundeni Clinical Institute, University of Bucharest, Romania.
Razvan
R
Iacob
Speranta
S
Iacob
Anca
A
Nastase
Codruta
C
Vagu
Ana Maria
AM
Ene
Alexandrina
A
Constantinescu
Daniela
D
Anghel
Constanta
C
Banica
Liliana
L
Paslaru
Daniel
D
Coriu
Simona
S
Dima
Cristian
C
Gheorghe
Elena
E
Ionica
Liana
L
Gheorghe
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D055815:Young Adult
D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases