Haraguchi Y, Aparicio J M, Takiguchi M, Akaboshi I, Yoshino M, Mori M, Matsuda I
Department of Pediatrics, Kumamoto University Medical School, Japan.
J Clin Invest. 1990 Jul;86(1):347-50. doi: 10.1172/JCI114707.
Argininemia results from a deficiency of arginase (EC 3.5.3.1), the last enzyme of the urea cycle in the liver. We examined the molecular basis for argininemia by constructing a genomic library followed by cloning and DNA sequencing. Discrete mutations were found on two alleles from the patient, a product of a nonconsanguineous marriage. There was a four-base deletion at protein-coding region 262-265 or 263-266 in exon 3 that would lead to a reading-frame shift after amino acid residue 87 and make a new stop codon at residue 132. The other was a one-base deletion at 77 or 78 in exon 2 that would lead to a reading-frame shift after residue 26 and make a stop codon at residue 31. For confirmation, genomic DNAs from the patient and from her parents were amplified by the polymerase chain reaction method. The patient was shown to be a compound heterozygote, inheriting an allele with the four-base deletion from the father and the other allele with the one-base deletion from the mother. These data seem to be the first evidence of a case of argininemia caused by two different deletion mutations.
精氨酸血症是由于肝脏中尿素循环的最后一种酶——精氨酸酶（EC 3.5.3.1）缺乏所致。我们通过构建基因组文库，随后进行克隆和DNA测序，研究了精氨酸血症的分子基础。在一位非近亲结婚患者的两个等位基因上发现了离散突变。外显子3的蛋白质编码区262 - 265或263 - 266处有一个四碱基缺失，这将导致87位氨基酸残基后阅读框移位，并在132位残基处产生一个新的终止密码子。另一个是外显子2中77或78位的一个碱基缺失，这将导致26位残基后阅读框移位，并在31位残基处产生一个终止密码子。为了进行确认，采用聚合酶链反应方法扩增了患者及其父母的基因组DNA。结果显示该患者为复合杂合子，从父亲那里继承了一个带有四碱基缺失的等位基因，从母亲那里继承了另一个带有一碱基缺失的等位基因。这些数据似乎是由两种不同缺失突变导致精氨酸血症病例的首个证据。
