Korean J Med.  1999 Nov;57(5):881-895.

Analysis of low - density - lipoprotein receptor gene in Korean patients with familial hypercholesterolemia

• Kim HS
• Chae IH
• Park YB
• Choe SC
• Han KH
• Chae JJ
• Kim SH

Abstract

Familial hypercholesterolemia (FH) is a common autosomal dominant disorder caused by a defect in the low-density-lipoprotein (LDL) receptor, disrupting the normal control of cholesterol metabolism. We have collected 86 FH families for over 5 years who met following Dx criteria 1) hypercholesterolemia over 280 mg/dl 2) Achilles tendon xanthoma thicker than 9 mm, and 3) familial tendency, and characterized the pattern of mutations in Korea FH patients. METHOD: Mutation was screened with linkage analysis into two ways; large structural rearrangements were screened by genomic Southern blotting or long-PCR technique, and small structural rearrangements were screened by PCR of each exon followed by SSCP analysis. The exact mutation sites were confirmed by sequencing. RESULT: 1) Large mutation: Three different large deletions(FH110, FH29, FH32) were found in 7(11.5%) among 61 families screened. FH110 was a deletion of 5.7kb from intron 8 to 12, which was found in 5 unrelated families. FH29 was a deletion of 3.8kb from intron 6 to 8, and FH32 was a deletion of 2kb from intron 6 to 7. These three deletions have not been reported previously. The mechanism of deletion was unequal crossover from mispairing Alu-sequences. 2) Small or point mutations: Nineteen different small mutations were found in 19(31.4%) among 86 families screened . These mutations comprised 9 missense, 3 nonsense, 2 splicing mutations, 3 small deletions, and 2 small insertions. One missense mutation (Pro664Leu) was found in 6 unrelated families. Among these mutations, 12 have not been reported previously. CONCLUSIONS: LDL receptor gene mutations are heterogeneous in Korean FH patients. We could not observe founder mutation but detect common mutations.

Keyword

Familial hypercholesterolemia; LDL-receptor gene mutation

MeSH Terms

Achilles Tendon
Blotting, Southern
Cholesterol
Exons
Humans
Hypercholesterolemia
Hyperlipoproteinemia Type II*
Introns
Korea
Lipoproteins*
Metabolism
Mutation, Missense
Point Mutation
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Receptors, LDL
Receptors, Lipoprotein*
Xanthomatosis
Cholesterol
Lipoproteins
Receptors, LDL
Receptors, Lipoprotein