Yorifuji T, Muroi J, Uematsu A, Tanaka K, Kiwaki K, Endo F, Matsuda I, Nagasaka H, Furusho K
Department of Pediatrics and Transplantation, Kyoto University Hospital, Japan.
Clin Genet. 1998 Oct;54(4):349-53. doi: 10.1034/j.1399-0004.1998.5440415.x.
Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It is X-linked and hemizygous new-born males usually suffer fatal hyperammonemia. In contrast, carrier females manifest variable phenotypes, ranging from asymptomatic carriers to those with severe hyperammonemia. In order to understand the correlation between X-inactivation status and the clinical phenotype of carrier females with this disorder, we analyzed the X-inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and two daughters with severe manifestation. In addition, we obtained tissue samples from various parts of the liver of one of these daughters and analyzed X-inactivation patterns and the residual OTC activities. The X-inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype. However, the X-inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. Interestingly, the degree of X-inactivation varied considerably, even within the same liver.
鸟氨酸转氨甲酰酶（OTC）缺乏症是最常见的尿素循环障碍。它是X连锁的，半合子新生男性通常会患致命性高氨血症。相比之下，携带致病基因的女性表现出不同的表型，从无症状携带者到严重高氨血症患者。为了了解X染色体失活状态与患有这种疾病的携带致病基因女性临床表型之间的相关性，我们分析了一个家庭中外周血白细胞的X染色体失活模式，该家庭由一名临床正常的母亲和两名表现严重的女儿组成。此外，我们从其中一名女儿的肝脏不同部位获取了组织样本，并分析了X染色体失活模式和残余的OTC活性。在这些携带致病基因的女性中，外周血白细胞的X染色体失活几乎是随机的，并且与疾病表型无关。然而，肝脏中的X染色体失活偏向性更强，并且与所有样本的OTC活性密切相关。有趣的是，即使在同一肝脏内，X染色体失活的程度也有很大差异。
