Abstract | BACKGROUND: OBJECTIVE: Our aim was to examine whether the c.2579C>T (p.A860V) variant of the LDLR gene affects the phenotype of FH. We present 2 index cases harboring biallelic LDLR variants, including the c.2579C>T (p.A860V) variant, which is defined as having uncertain significance in ClinVar. METHODS: RESULTS: In one family, the index case involved a patient who harbored biallelic A860V and c.1528-1529insA (p.T510Nfs) LDLR variants and had 8 children; the affected children had the p.T510Nfs variant, and the unaffected children had the A860V variant. In another family, the patient involved in the index case and his sister had biallelic A860V and c.1845+2T>C LDLR variants. There was no difference in FH phenotype between these siblings and their relatives who were heterozygous for the c.1845+2T>C variant. In addition, the allele frequency of the A860V variant (0.0062/0.0095) in the Japanese population, as indicated by 2 databases, was higher than expected based on the prevalence of heterozygous FH in the Japanese population (0.002-0.005). CONCLUSIONS: This is the first report to show using pedigree-based genetic analysis that the A860V variant of the LDLR gene is a benign variant.
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Authors | Mika Hori, Eiji Miyauchi, Cheol Son, Mariko Harada-Shiba |
Journal | Journal of clinical lipidology
(J Clin Lipidol)
2019 Mar - Apr
Vol. 13
Issue 2
Pg. 335-339
ISSN: 1933-2874 [Print] United States |
PMID | 30745271
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Adolescent
- Child
- Female
- Gene Frequency
- Humans
- Hyperlipoproteinemia Type II
(genetics, pathology)
- Male
- Middle Aged
- Pedigree
- Phenotype
- Polymorphism, Single Nucleotide
- Receptors, LDL
(genetics)
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