Analysis of low - density - lipoprotein receptor gene in Korean patients with familial hypercholesterolemia / 대한내과학회지
Korean Journal of Medicine
;
: 881-895, 1999.
Article
in Korean
| WPRIM
| ID: wpr-139242
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Achilles Tendon
/
Receptors, LDL
/
Introns
/
Xanthomatosis
/
Blotting, Southern
/
Polymerase Chain Reaction
/
Exons
/
Cholesterol
/
Point Mutation
/
Receptors, Lipoprotein
Limits:
Humans
Country/Region as subject:
Asia
Language:
Korean
Journal:
Korean Journal of Medicine
Year:
1999
Type:
Article
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