Quelhas D, Quental R, Vilarinho L, Amorim A, Azevedo L
IGMJM - Institute of Medical Genetics Jacinto de Magalhães, Porto, Portugal.
Ann Hum Genet. 2007 May;71(Pt 3):348-53. doi: 10.1111/j.1469-1809.2006.00334.x. Epub 2006 Dec 12.
Congenital Disorders of Glycosylation (CDG) are a group of recessive genetic disorders characterized by hypoglycosylation of glycoproteins. CDG-Ia, the most common type, is caused by mutations in the PMM2 gene, coding for a phosphomannomutase (PMM2; EC 5.4.2.8). The mutational spectrum of PMM2 comprises more than 80 different mutations but one of them, R141H, is particularly interesting due to its high frequency among CDG-Ia patients worldwide. In contrast, other mutations are ethnically or geographically restricted, such as D65Y which is only found in patients of Iberian ancestry. In the present study a population genetic approach was used in an attempt to clarify the origins of two important disease causing mutations: R141H and D65Y. Based on SNP and STR genotypic analysis, we ascertained an association between the R141H substitution and a particular haplotype, suggesting a common origin for all the mutated chromosomes. Similar results were found for D65Y, although the associated haplotype was different from that of R141H, suggesting independent origins for these two mutations. Our results enable us to infer an Iberian origin for the D65Y mutation.
糖基化先天性疾病（CDG）是一组隐性遗传疾病，其特征是糖蛋白低聚糖化。最常见的类型CDG-Ia是由PMM2基因突变引起的，该基因编码磷酸甘露糖变位酶（PMM2；EC 5.4.2.8）。PMM2的突变谱包含80多种不同的突变，但其中一种R141H特别有趣，因为它在全球CDG-Ia患者中出现的频率很高。相比之下，其他突变在种族或地理上受到限制，例如D65Y仅在伊比利亚血统的患者中发现。在本研究中，采用群体遗传学方法试图阐明两个重要致病突变R141H和D65Y的起源。基于单核苷酸多态性（SNP）和短串联重复序列（STR）基因型分析，我们确定R141H替代与特定单倍型之间存在关联，这表明所有突变染色体都有共同的起源。D65Y也得到了类似的结果，尽管相关单倍型与R141H不同，这表明这两个突变有独立的起源。我们的结果使我们能够推断D65Y突变起源于伊比利亚。
