Varret M, Abifadel M, Rabès J-P, Boileau C
INSERM U781, Hôpital Necker-Enfants Malades, Université Paris 5 - René Descartes, Paris, France.
Clin Genet. 2008 Jan;73(1):1-13. doi: 10.1111/j.1399-0004.2007.00915.x. Epub 2007 Nov 16.
Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated elevation of plasmatic low-density lipoprotein cholesterol associated with high risk of premature cardiovascular complications. More than 1000 mutations in the LDLR gene and 9 in the APOB gene have been implicated. We have shown further heterogeneity with the discovery of missense mutations in the PCSK9 gene resulting in ADH. Different studies have tried to evaluate the respective contribution of mutations in each gene to the disease, but results were not always in agreement. After a brief overview of mutations reported for each gene, strategies and results of these different studies are reviewed and analyzed. Altogether, numerous reports give evidence for the existence of a greater level of genetic heterogeneity in ADH and the involvement of still unknown genes.
常染色体显性高胆固醇血症（ADH）的特征是血浆低密度脂蛋白胆固醇单独升高，并伴有过早发生心血管并发症的高风险。已发现LDLR基因中有1000多个突变，APOB基因中有9个突变。我们通过在PCSK9基因中发现导致ADH的错义突变，进一步证明了其异质性。不同的研究试图评估每个基因中的突变对该疾病的各自贡献，但结果并不总是一致。在简要概述每个基因报道的突变后，对这些不同研究的策略和结果进行了综述和分析。总之，大量报告证明ADH存在更高水平的遗传异质性，并且仍有未知基因参与其中。
