IngentaConnect Three novel small deletion mutations of the LDL receptor gene in ...

Authors: Chae, Jae Jin¹; Kim, Sung Han²; Kim, Un Kyung¹; Han, Ki-Hoon³; Kim, Hyo-Soo³; Kastner, Daniel L.⁴; Namkoong, Yong⁵; Park, Young-Bae³; Lee, Chung Choo²

Source: Clinical Genetics, Volume 55, Number 5, May 1999 , pp. 325-331(7)

Publisher: Blackwell Publishing

Abstract:

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.

Keywords: FH; LDL receptor gene; SSCP; three small deletion mutations

Document Type: Research article

DOI: 10.1034/j.1399-0004.1999.550505.x

Affiliations: 1: Department of Molecular Biology, Seoul National University, Seoul, South Korea, 2: Department of Biology and SRC for Cell Differentiation, Seoul National University, Seoul 151-742, South Korea, 3: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea, 4: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA, 5: Department of Biology, Kangnung National University, Kangnung, South Korea

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Three novel small deletion mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia