Journal Articles European Journal of Human Genetics Year : 2010

A fourth locus for Autosomal Dominant Hypercholesterolemia maps at 16q22.1

Yassine Zair
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Abstract

Autosomal Dominant Hypercholesterolemia (ADH) is characterized by isolated elevation of plasmatic LDL cholesterol 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 theses three genes was excluded. A genomewide scan mapped the disease-causing gene, named HCHOLA4, at 16q22.1 in a 7.89 Mb interval containning 154 genes with a maximum lod-score of 3.9. To reduce the linked region, we genotyped 18 smaller nonLDLR/nonAPOB/nonPCSK9-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 analysed 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 since 9 families were neither linked to the LDLR, APOB, PCSK9 genes nor the new HCHOLA4 locus.

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hal-00549893 , version 1 (23-12-2010)

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Mathilde Varret, Alice Marques-Pinheiro, Marie Marduel, Jean-Pierre Rabès, Martine Devillers, et al.. A fourth locus for Autosomal Dominant Hypercholesterolemia maps at 16q22.1. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.94⟩. ⟨hal-00549893⟩
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