Description
The A480V pathogenic variant in the LDLR gene has been reported in the homozygous state in a Chinese male with disease manifestation at less than 10 years of age. The A480V variant segregated with disease in at least three heterozygous family members, all of whom demonstrated a milder phenotype (Lin et. al., 2008). The A480V variant has also been reported in two other patients with clinical signs of FH, including one proband with severe hypercholesterolemia at young age who was compound heterozygous for a W577G variant (Brusgaard et al., 2006; Jiang et al., 2016). The A480V variant resides within the LDL-receptor class B 2 repeat and results in a conservative amino acid substitution at a position that is highly conserved across species. In addition, functional analysis of homozygous LDLR expression demonstrated that, compared to normal controls, A480V LDLR expression, binding ability, and up-taking ability was 39%, 63%, and 76% respectively; heterozygous function was also shown to be impaired to a lesser degree (Lin et al., 2008). Finally, the A480V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
