Aalto-Setälä K, Koivisto U M, Miettinen T A, Gylling H, Kesäniemi Y A, Savolainen M, Pyörälä K, Ebeling T, Mononen I, Turtola H
Institute of Biotechnology, University of Helsinki, Finland.
J Intern Med. 1992 Mar;231(3):227-34. doi: 10.1111/j.1365-2796.1992.tb00528.x.
In order to determine the prevalence of major rearrangements of the low density lipoprotein (LDL) receptor gene in Finland, DNA samples of 199 unrelated Finnish patients with the heterozygous form of familial hypercholesterolaemia (FH) were examined by Southern blot analysis. The FH-Helsinki mutation, characterized by a 9.5-kb deletion in the 3'-end of the LDL receptor gene, was found in 75 (38%) of the patients. The prevalence of this mutation ranged from 26-58% in different areas of Finland. A striking exception was the North Karelia region, where only one out of 26 (4%) FH patients was found to carry the FH-Helsinki allele. Two patients were found to carry other types of large nucleotide rearrangements of the LDL receptor gene. One mutation was a 7.5-kb deletion eliminating exons 7 to 10, and the other was a 13-kb deletion covering exons 11 to 16 of the LDL receptor gene. Serum lipoprotein levels were very similar in each category of mutation, i.e. in patients with the FH-Helsinki gene, those with the two other types of deletion, and the remaining patients with as yet unknown types of LDL receptor gene defects. These results show that, even in genetically uniform populations, FH may be heterogeneous at the DNA level. DNA techniques enable an unequivocal diagnosis for almost 40% of the Finnish patients with the heterozygous form of FH.
为了确定芬兰低密度脂蛋白（LDL）受体基因主要重排的患病率，通过Southern印迹分析检测了199名患有杂合型家族性高胆固醇血症（FH）的不相关芬兰患者的DNA样本。在75名（38%）患者中发现了FH - 赫尔辛基突变，其特征是LDL受体基因3'端有一个9.5kb的缺失。该突变在芬兰不同地区的患病率为26% - 58%。一个显著的例外是北卡累利阿地区，在26名FH患者中只有1名（4%）被发现携带FH - 赫尔辛基等位基因。发现两名患者携带LDL受体基因的其他类型的大核苷酸重排。一种突变是7.5kb的缺失，消除了外显子7至10，另一种是13kb的缺失，覆盖了LDL受体基因的外显子11至16。每类突变患者的血清脂蛋白水平非常相似，即携带FH - 赫尔辛基基因的患者、携带其他两种缺失类型的患者以及其余LDL受体基因缺陷类型未知的患者。这些结果表明，即使在基因同质的人群中，FH在DNA水平上也可能是异质的。DNA技术能够对近40%的芬兰杂合型FH患者做出明确诊断。
