Funghini S, Donati M A, Pasquini E, Zammarchi E, Morrone A
Metabolic and Neuromuscular Unit, Department of Pediatrics, University of Florence, Florence, Italy.
Hum Mutat. 2003 Oct;22(4):340-1. doi: 10.1002/humu.9184.
Carbamyl Phosphate Synthetase I deficiency (CPSID) is a rare autosomal recessive urea cycle disorder usually characterized by potentially lethal neonatal hyperammonemia. The large (5215 bp) CPS1-cDNA, expressed only in liver and epithelial cells of intestinal mucosa, has been cloned. Until now the CPS1 genomic organization was unknown. Taking advantage of the phylogenetic lineage between the CPS1 gene of Homo sapiens and Rattus norvegicus, we determined the intron-exon organization of the human CPS1 gene. Starting from the ATG codon, the CPS I gene is organized in 38 exons spanning from 50bp to 200 bp. We also report the molecular studies on an Italian patient affected by neonatal CPSD. Two novel genetic lesions (c.1370T>G and c.2429A>G) that lead to the novel amino acid substitutions V457G and Q810R, and the known N1406T polymorphism, were detected in the patient's CPS1 RNA and in genomic DNA isolated from peripheral blood lymphocytes. The characterization of the CPS1 genomic organization will allow the identification of the genetic lesions of CPSD patients, the detection of carriers, better genetic counseling and a more certain, less invasive method of prenatal diagnosis.
氨甲酰磷酸合成酶I缺乏症（CPSID）是一种罕见的常染色体隐性尿素循环障碍疾病，通常表现为具有潜在致死性的新生儿高氨血症。仅在肝脏和肠黏膜上皮细胞中表达的大的（5215 bp）CPS1 - cDNA已被克隆。到目前为止，CPS1的基因组结构尚不清楚。利用智人与褐家鼠CPS1基因之间的系统发育谱系，我们确定了人类CPS1基因的内含子 - 外显子结构。从起始密码子ATG开始，CPS I基因由38个外显子组成，长度从50bp到200bp不等。我们还报告了对一名患有新生儿CPSD的意大利患者的分子研究。在患者的CPS1 RNA和从外周血淋巴细胞分离的基因组DNA中检测到两个导致新的氨基酸取代V457G和Q810R的新的基因病变（c.1370T>G和c.2429A>G），以及已知的N1406T多态性。CPS1基因组结构的表征将有助于识别CPSD患者的基因病变、检测携带者、提供更好的遗传咨询以及一种更确定、侵入性更小的产前诊断方法。
