Chae J J, Kim S H, Kim U K, Han K H, Kim H S, Kastner D L, Namkoong Y, Park Y B, Lee C C
Department of Molecular Biology, Seoul National University, South Korea.
Clin Genet. 1999 May;55(5):325-31. doi: 10.1034/j.1399-0004.1999.550505.x.
The low-density lipoprotein (LDL) receptor gene from 80 unrelated Korean patients with familial hypercholesterolemia (FH) was analyzed to screen for small structural rearrangements that could not be detected by Southern blot hybridization. Three different small deletions were detected in exon 11 of 3 FH patients and were characterized by DNA sequence analysis. Of them two mutations are in-frame 36-bp (FH 2) and 9-bp (FH 34) deletions that result in the loss of twelve amino acids (from Met510 to Ile521) and three amino acids (Thr513, Asp514 and Trp515), respectively. Both mutations are located in the third of the five YWTD motifs of the LDL receptor gene. The third mutation (FH 400) is a 2-bp deletion that shifts the translational reading frame and results in a prematurely terminated receptor protein. The generation of a 36-bp deletion can be explained by the formation of a hairpin-loop structure mediated by inverted repeat sequences. On the other hand, the mechanism responsible for the 9- and the 2-bp deletions is probably strand-slippage mispairing mediated by short direct repeats. All of these three deletions are novel mutations. Each of the three deletions was detected only in a single pedigree out of 80 FH families analyzed.
对80名无亲缘关系的韩国家族性高胆固醇血症（FH）患者的低密度脂蛋白（LDL）受体基因进行分析，以筛查无法通过Southern印迹杂交检测到的小结构重排。在3名FH患者的第11外显子中检测到3种不同的小缺失，并通过DNA序列分析对其进行了表征。其中两种突变是框内36 bp（FH 2）和9 bp（FH 34）缺失，分别导致12个氨基酸（从Met510到Ile521）和3个氨基酸（Thr513、Asp514和Trp515）的缺失。这两种突变均位于LDL受体基因五个YWTD基序中的第三个。第三种突变（FH 400）是2 bp缺失，它会改变翻译阅读框并导致受体蛋白过早终止。36 bp缺失的产生可以通过由反向重复序列介导的发夹环结构的形成来解释。另一方面，导致9 bp和2 bp缺失的机制可能是由短直接重复序列介导的链滑动错配。这三种缺失均为新突变。在分析的80个FH家族中，这三种缺失中的每一种仅在一个家系中被检测到。
