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Three novel small deletion mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia
Author(s) -
Chae Jae Jin,
Kim Sung Han,
Kim Un Kyung,
Han KiHoon,
Kim HyoSoo,
Kastner Daniel L.,
Namkoong Yong,
Park YoungBae,
Lee Chung Choo
Publication year - 1999
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.1999.550505.x
Subject(s) - familial hypercholesterolemia , genetics , gene , mutation , ldl receptor , medicine , biology , endocrinology , cholesterol , lipoprotein
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 Met 510 to Ile 521 ) and three amino acids (Thr 513 , Asp 514 and Trp 515 ), 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.