Lelli N, Ghisellini M, Calandra S, Gaddi A, Ciarrocchi A, Coviello D A, Bertolini S
Istituto di Patologia Generale, Università di Modena, Italy.
Hum Genet. 1991 Feb;86(4):359-62. doi: 10.1007/BF00201833.
During a survey of Italian patients with familial hypercholesterolemia (FH), we identified an FH heterozygous patient with a gross rearrangement of the low density lipoprotein (LDL) receptor gene. Southern blot analysis of the proband's DNA digested with restriction enzymes PvuII, BamHI, BglII and XbaI and hybridization with cDNA probes complementary to the 3' end of the gene revealed the presence of abnormal fragments that were approximately 7 kb larger than their normal counterparts. DNA digestion with other enzymes (EcoRV, NcoI, KpnI and StuI) and hybridization with probes complementary to exons 13-17 generated normal fragments and an abnormal fragment of 6.3-6.8 kb. These results are consistent with the presence of an insertion of approximately 7 kb caused by a duplication of exons 13, 14 and 15. This is a novel mutation that is most probably the result of an unequal crossing-over between repetitive sequences located in intron 12 and intron 15. This novel mutation has been designated FHBologna 2.
在一项对意大利家族性高胆固醇血症（FH）患者的调查中，我们鉴定出一名FH杂合子患者，其低密度脂蛋白（LDL）受体基因发生了大片段重排。用限制性内切酶PvuII、BamHI、BglII和XbaI消化先证者的DNA，并与与该基因3'端互补的cDNA探针杂交，结果显示存在异常片段，这些片段比其正常对应片段大约大7 kb。用其他酶（EcoRV、NcoI、KpnI和StuI）消化DNA，并与与外显子13 - 17互补的探针杂交，产生了正常片段和一个6.3 - 6.8 kb的异常片段。这些结果与外显子13、14和15重复导致大约7 kb插入的情况一致。这是一种新的突变，很可能是位于内含子12和内含子15中的重复序列之间不等交换的结果。这种新的突变被命名为FHBologna 2。
