Ann Hematol (2005) 84: 646–649
DOI 10.1007/s00277-005-1048-y
SHORT COMMUNICATION
Halis Simsek
.
Yasemin H. Balaban
.
Engin Yilmaz
.
Hale Sumer
.
Yahya Buyukasik
.
Cem Cengiz
.
Osman Ozcebe
.
Gulsen Hascelik
.
Gonca Tatar
Mutations of the HFE gene among Turkish hereditary
hemochromatosis patients
Received: 21 January 2005 / Accepted: 8 April 2005 / Published online: 4 May 2005
# Springer-Verlag 2005
Abstract Since the discovery of the HFE gene, C282Yand
H63D mutations have been reported as significantly cor-
related with clinically manifested hereditary hemochroma-
tosis (HH). As the other genes involved in iron metabolism
have been described, non-HFE cases of HH have been iden-
tified. Since in the general Turkish population, the C282Y
mutation is not found and the H63D mutation is of high
frequency, we aimed to determine mutations in the HFE
genes in our patients with HH. The HFE gene of the five
patients with HH were sequenced. C282Y mutation was
absent, and all HH patients were heterozygote for H63D
mutation. No other mutation was found in HFE gene by
sequencing. Although the higher allele frequency of the
H63D mutation in Turkish HH patients than in the general
population implies a role of the H63D mutation in iron
overload, there is a strong possibility that Turkish HH pa-
tients have non-HFE hemochromatosis.
Keywords Hereditary hemochromatosis
.
HFE gene
.
H63D mutation
.
Sequence analysis
Introduction
Hereditary hemochromatosis (HH) is the most common
autosomal recessive disorder affecting the white adult pop-
ulation, particularly those of northern European descent of
Celtic ancestry [1]. Although patients with cirrhosis may
develop liver cancer irrespective of sufficient treatment, the
appropriate intervention by phlebotomy at early stage of
disease prevents all manifestations of the disease, except for
arthropathy [2–4]. Identification of the HFE gene in 1996
[5] created enthusiasm for screening populations for this po-
tentially preventable disease. Among the 37 allele variants
of HFE described [6], two mutations, C282Y and H63D,
are significantly correlated with clinically manifested HH.
Although the majority (80–100%) of HH cases in the
western world and in northern Europe are associated with
these two mutations, there are cases of HH in whom neither
the C282Y nor the H63D mutation was found [7–9]. In
fact, the allele frequency of the C282Y mutation declines
from northern to southern Europe, in contrast to the allele
frequencies of the H63D mutation. Therefore, while the
proportion of homozygotes for the C282Y mutation is
higher in northern Europe, the proportion of the compound
heterozygote, in which one copy each of the C282Y and
H63D mutations is inherited on separate chromosomes, is
higher in southern Europe [10–13]. Bauder et al. [14]
showed that C282Y mutation was underrepresented, where-
as prevalence of H63D mutation was highest in patients
from French Basque Country with HH compared with
H. Simsek
.
Y. H. Balaban
.
G. Tatar
Unit of Gasroenterology,
Hacettepe University,
Ankara, Turkey
E. Yilmaz
Department of Medical Biology,
Hacettepe University,
Ankara, Turkey
H. Sumer
Department of Internal Medicine,
Hacettepe University,
Ankara, Turkey
Y. Buyukasik
.
O. Ozcebe
Unit of Hematology,
Hacettepe University,
Ankara, Turkey
C. Cengiz
Unit of Gastroenterology,
Yuksek Ihtisas Hospital,
Ankara, Turkey
G. Hascelik
Unit of Microbiology and Clinical Microbiology,
Hacettepe University,
Ankara, Turkey
H. Simsek (*)
Cinnah Caddesi no. 110/3,
Cankaya, Ankara, Turkey
e-mail: hsimsek@hacettepe.edu.tr
Tel.: +90-312-4423715
Fax: +90-312-4422161