Random X inactivation resulting in mosaic nullisomy of region Xp21.1----p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease.
Random X inactivation resulting in mosaic nullisomy of region Xp21.1----p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease.
复制标题
随机 X 失活导致 Xp21.1----p21.3 区域嵌合无效，与鸟氨酸转氨甲酰酶缺乏症和慢性肉芽肿病的杂合性相关。
DOI：
10.1159/000132078
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Francke,U
中科院分区：
文献类型：
--
作者：
Francke,U
一名性腺发育正常、轻度智力发育迟滞的年轻女性，发现Xp21条带大部分新发间质缺失，核型为46，X, del(X) （pter→p21.3::p21.1→qter）。淋巴细胞和皮肤成纤维细胞的复制研究显示，在45%的细胞中，正常X是晚期复制的。获得了她的成纤维细胞与hprt缺陷的中国仓鼠细胞之间的体细胞杂交，并选择了是否保留活跃的人类X染色体。在几个独立杂交种中，缺失的X保留在活性状态。部分鸟氨酸氨基甲酰基转移酶（鸟氨酸氨基甲酰转移酶EC 2.1.3.3） （OTC）缺乏症表现为在蛋白质负荷后尿中乳酸排泄量升高和血清谷氨酰胺升高。这证实了OTC的结构基因与这种缺失的关系。中性粒细胞功能检测显示慢性肉芽肿病（CGD）的杂合性，表明CGD基因在缺失中定位。因此，X失活嵌合体也存在于肝细胞和中性粒细胞中。随机X失活的女性与Xp缺失以前没有报道。来自该患者的细胞和含有她缺失的正常X染色体的体细胞杂交体为X连锁基因的精确定位和人类X染色体短臂上的DNA序列提供了材料。
A young woman with normal gonadal development and mild mental retardation was found to have a small de novo interstitial deletion of most of band Xp21, karyotype designation 46, X, del(X) (pter→p21.3::p21.1→qter). Replication studies on lymphocytes and skin fibroblasts revealed that in 45% of cells the normal X was late replicating. Somatic cell hybrids between her fibroblasts and HPRT-deficient Chinese hamster cells were obtained and selected for and against retention of the active human X chromosome. In several independent hybrids the deleted X was retained in the active state. Partial ornithine transcarbamylase (ornithine carbamoyltransferase EC 2.1.3.3) (OTC) deficiency was documented by elevated urinary orotic acid excretion and increased serum glutamine after a protein load. This confirms the mapping of the structural gene for OTC to this deletion. Testing of neutrophil function revealed heterozygosity for chronic granulomatous disease (CGD) suggesting that a gene for CGD maps within the deletion. Thus, X inactivation mosaicism is also present in hepatocytes and neutrophilic granulocytes. Random X inactivation in a female with an Xp deletion has not been previously reported. The cells from this patient and the somatic cell hybrids containing her deleted X chromosome in the absence of the normal X provide material for the precise mapping of X linked genes and DNA sequences on the short arm of the human X chromosome.