Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity
Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity
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DOI：
10.1006/bcmd.2000.0292
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发表时间：
2000-04-01
影响因子：
2.3
通讯作者：
Loukopoulos, D
中科院分区：
文献类型：
--
作者：
Papanikolaou, G;Politou, M;Loukopoulos, D
遗传性血色沉着症(HH)在高加索人中很常见；报告的发病率从0.3%到0.8%不等。1996年发现了一个候选HFE基因，随后很快描述了两个祖先突变，即C.845G->；A(C282Y)和C.187C->；G(H63D)。最近又增加了突变S65C，这可能代表了一种简单的多态。HH在希腊的发病率尚不清楚，但临床病例很少。同样未知的是这两个突变等位基因的携带者频率。本报告对后者作了初步估计。它基于10名希腊血统无关患者的基因分析数据，这些患者被转介到我们的基因分型中心，以及158名未经挑选的男性献血者。C282Y和H63D突变的等位基因频率分别为0.003和0.145。在50%的HH患者中检测到C282Y等位基因。这比美国(82%)和法国(91%)报道的HH患者的发病率低得多，更接近意大利的报道(%)。5名患者没有携带任何已知的HFE突变；3名患者可能代表青少年血色素沉着症，因为他们起病较早，铁负荷过高，性腺功能减退和心脏病。我们认为，遗传异质性在南欧更为突出。也有可能的是，负责基因的外显性在地中海的另一边是不同的。(C)2000年学术出版社。
Hereditary hemochromatosis (HH) is common among Caucasians; reported disease frequencies vary from 0.3 to 0.8%. Identification of a candidate HFE gene in 1996 was soon followed by the description of two ancestral mutations, i.e., c.845G --> A (C282Y) and c.187C --> G (H63D). To these was recently added the mutation S65C, which may represent a simple polymorphism. The incidence of HH in Greece is unknown but clinical cases are rare. Also unknown is the carrier frequency of the two mutant alleles. A first estimate of the latter is given in the present report. It is based on data from the genetic analysis of 10 unrelated patients of Greek origin who were referred to our center for genotyping and 158 unselected male blood donors. The allele frequencies for the C282Y and H63D mutations were 0.003 and 0.145, respectively. The C282Y allele was detected in 50% of HH patients. This is considerably lower than the frequencies reported for HH patients in the U.S.A. (82%) and France (91%) and closer to that reported in Italy (64%). Five patients did not carry any known HFE mutation; three may represent cases of juvenile hemochromatosis, given their early onset with iron overload, hypogonadism, and heart disease. We suggest that genetic heterogeneity is more prominent in Southern Europe. It is also possible that the penetrance of the responsible genes is different across the Mediterranean. (C) 2000 Academic Press.