Craig J E, Rochette J, Sampietro M, Wilkie A O, Barnetson R, Hatton C S, Demenais F, Thein S L
Department of Clinical Genetics, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Blood. 1997 Jul 1;90(1):428-34.
A large English pedigree in which heterocellular hereditary persistence of fetal hemoglobin (HPFH) segregates is described. beta-globin cluster deletions and gamma gene promoter mutations associated with HPFH have been excluded. Of particular importance in this pedigree is the absence of any cosegregating hemoglobinopathy, thus allowing observation of the segregation pattern of this form of HPFH without the complicating effect of a beta-globin gene mutation. Information gained in this study confirms that the extent of elevation of hemoglobin (Hb) F and F cells varies between affected individuals. There are one example of incomplete penetrance and three examples of father-to-son transmission, thus excluding X-linked inheritance. Consistent with previous reports, the most likely mode of inheritance is autosomal codominant. Linkage studies using a beta-globin cluster microsatellite show no evidence of linkage to this chromosomal region implicating the presence of trans-acting regulatory factor(s). We have recently mapped one such locus to the chromosome 6q region in a very large Asian-Indian pedigree. Linkage to chromosome 6q in the English pedigree was excluded, thus indicating the presence of genetic heterogeneity in heterocellular HPFH.
本文描述了一个大型英国家系，其中异细胞遗传性胎儿血红蛋白持续存在（HPFH）呈分离状态。与HPFH相关的β-珠蛋白基因簇缺失和γ基因启动子突变已被排除。在这个家系中特别重要的是不存在任何共分离的血红蛋白病，因此可以观察到这种形式的HPFH的分离模式，而不受β-珠蛋白基因突变的复杂影响。本研究获得的信息证实，受影响个体之间血红蛋白（Hb）F和F细胞的升高程度有所不同。有一个不完全外显的例子和三个父子传递的例子，因此排除了X连锁遗传。与先前的报道一致，最可能的遗传方式是常染色体共显性。使用β-珠蛋白基因簇微卫星进行的连锁研究没有显示与该染色体区域连锁的证据，这意味着存在反式作用调节因子。我们最近在一个非常大的亚洲印度家系中将一个这样的基因座定位到了6号染色体q区域。英国家系中与6号染色体q的连锁被排除，因此表明异细胞HPFH存在遗传异质性。
