Cartwright G E, Edwards C Q, Kravitz K, Skolnick M, Amos D B, Johnson A, Buskjaer L
N Engl J Med. 1979 Jul 26;301(4):175-9. doi: 10.1056/NEJM197907263010402.
Previous studies have shown that hemochromatosis is an inherited, autosomal-recessive disease and that the gene is closely linked to the HLA locus on chromosome 6. We obtained a lod score for linkage of +9.8 for a recombination fraction of 0.0 and a gene frequency of 0.056, the frequency estimated in this population. We studied the phenotypic expression of the disease in 261 members of 10 pedigrees. In heterozygotes over 20 years of age, there was an intermediate increase in transferrin saturation and a limited increase in hepatic iron but no clinical manifestations. In male heterozygotes, the average amount of iron in the liver increased from about 0.2 to 1.3 g. Abnormal homozygotes accumulated iron progressively with time, with men accumulating about 18 g in the liver. All measurements of iron status were increased in abnormal homozygotes. Hemochromatosis is inherited as an autosomal-recessive disease, with partial biochemical expression in heterozygotes.
先前的研究表明，血色素沉着症是一种遗传性常染色体隐性疾病，该基因与6号染色体上的HLA位点紧密连锁。对于重组率为0.0且基因频率为0.056（该人群中的估计频率），我们获得了连锁lod分数为+9.8。我们研究了10个家系中261名成员的疾病表型表达。在20岁以上的杂合子中，转铁蛋白饱和度有中度升高，肝脏铁含量有有限升高，但无临床表现。在男性杂合子中，肝脏中铁的平均含量从约0.2克增加到1.3克。异常纯合子随着时间的推移逐渐积累铁，男性肝脏中积累约18克。异常纯合子的所有铁状态测量值均升高。血色素沉着症作为常染色体隐性疾病遗传，杂合子有部分生化表达。
