Familial Mediterranean fever presenting as fever of unknown origin in Korea / 소아과

Familial Mediterranean fever (FMF) is the most common Mendelian autoinflammatory disease, characterized by uncontrolled activation of the innate immune system that manifests as recurrent brief fever and polyserositis (e.g., peritonitis, pleuritic, and arthritis). FMF is caused by autosomal recessive mutations of the Mediterranean fever gene, MEFV which encodes the pyrin protein. Although FMF predominantly affects people from Mediterranean and Middle Eastern ethnic origins, 3 cases of FMF have been reported in Korea since 2012. We report another case of FMF in Korea in which the patient presented with a month-long fever without serositis. After treatment with colchicine was initiated, the patient’s symptoms quickly subsided. The response to colchicine was helpful for diagnosis. We compare the FMF genotypes in Korea with in other countries. Studying FMF cases in Korea will help establish the best MEFV exons to use for screening and diagnosis of Korean FMF.

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

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.

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

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.