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A fourth locus for autosomal dominant hypercholesterolemia maps at 16q22.1
- Source :
- European Journal of Human Genetics, European Journal of Human Genetics, Nature Publishing Group, 2010, 〈10.1038/ejhg.2010.94〉, European Journal of Human Genetics, Nature Publishing Group, 2010, ⟨10.1038/ejhg.2010.94⟩
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
Abstract
- Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated increase in plasmatic low-density lipoprotein (LDL) cholesterol levels associated with high risk of premature cardiovascular disease. Mutations in LDLR, APOB, and PCSK9 genes have been shown to cause ADH. We now report further genetic heterogeneity of ADH through the study of a large French family in which the involvement of these three genes was excluded. A genome-wide scan mapped the disease-causing gene, named HCHOLA4, at 16q22.1 in a 7.89-Mb interval containing 154 genes with a maximum LOD score of 3.9. To reduce the linked region, we genotyped 18 smaller non-LDLR/non-APOB/non-PCSK9-ADH families at the HCHOLA4 locus. Six families did not exclude linkage to the locus, but none allowed reduction of the disease interval. The 154 regional genes were sorted according to the function of the encoded protein and tissue expression profiles, and 57 genes were analyzed through sequencing of their coding region and close flanking intronic parts. No disease-causing mutation was identified in these families, particularly in the LCAT gene. Finally, our results also show the existence of other ADH genes as nine families were neither linked to LDLR, APOB, and PCSK9 genes nor to the new HCHOLA4 locus.
- Subjects :
- Adult
Male
Adolescent
Apolipoprotein B
Genome-wide association study
Locus (genetics)
Article
Hyperlipoproteinemia Type II
Young Adult
Gene mapping
Genetics
Humans
Coding region
Genetic Predisposition to Disease
Child
Gene
Genetics (clinical)
lipoprotein metabolism
Aged, 80 and over
Family Health
hypercholesterolemia
biology
Genetic heterogeneity
Chromosome Mapping
Middle Aged
Pedigree
Child, Preschool
LDL receptor
biology.protein
Female
lipids (amino acids, peptides, and proteins)
genetic mapping
France
Lod Score
Chromosomes, Human, Pair 16
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 14765438 and 10184813
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....db1e3a4f6ef18debcea60f8248e92c8c