Postgraduate Program in Child and Adolescent Health, UFRGS, Porto Alegre, Brazil.
Orphanet J Rare Dis. 2010 May 28;5:14. doi: 10.1186/1750-1172-5-14.
Most lysosomal diseases (LD) are inherited as autosomal recessive traits, but two important conditions have X-linked inheritance: Fabry disease and Mucopolysaccharidosis II (MPS II). These two diseases show a very different pattern regarding expression on heterozygotes, which does not seem to be explained by the X-inactivation mechanism only. While MPS II heterozygotes are asymptomatic in most instances, in Fabry disease most of female carriers show some disease manifestation, which is sometimes severe. It is known that there is a major difference among X-linked diseases depending on the cell autonomy of the gene product involved and, therefore, on the occurrence of cross-correction. Since lysosomal enzymes are usually secreted and uptaken by neighbor cells, the different findings between MPS II and Fabry disease heterozygotes can also be due to different efficiency of cross-correction (higher in MPS II and lower in Fabry disease). In this paper, we review these two X-linked LD in order to discuss the mechanisms that could explain the different rates of penetrance and expressivity observed in the heterozygotes; this could be helpful to better understand the expression of X-linked traits.
大多数溶酶体贮积症（LD）为常染色体隐性遗传，但有两种重要的疾病为 X 连锁遗传：法布里病和黏多糖贮积症 II 型（MPS II）。这两种疾病在杂合子的表达模式上存在很大差异，这似乎不能仅用 X 染色体失活机制来解释。在大多数情况下，MPS II 杂合子无症状，但在法布里病中，大多数女性携带者表现出一些疾病表现，有时甚至很严重。已知 X 连锁疾病之间存在很大差异，这取决于所涉及的基因产物的细胞自主性，因此也取决于交叉校正的发生。由于溶酶体酶通常被分泌并被邻近细胞摄取，因此 MPS II 和法布里病杂合子之间的不同发现也可能是由于交叉校正的效率不同（MPS II 中较高，法布里病中较低）。本文综述了这两种 X 连锁 LD，以探讨可解释杂合子中观察到的不同外显率和表现度的机制；这有助于更好地理解 X 连锁性状的表达。
