Feldmann D, Rozet J M, Pelet A, Hentzen D, Briand P, Hubert P, Largilliere C, Rabier D, Farriaux J P, Munnich A
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12, Paris, France.
J Med Genet. 1992 Jul;29(7):471-5.
Ornithine transcarbamylase (OTC) deficiency is a frequent X linked disorder of the urea cycle which is responsible for lethal neonatal hyperammonaemia in males and for various clinical symptoms in heterozygous females. In order to improve the efficiency of our screening for mutant genotypes, we focused on molecular domains of functional or structural importance in the OTC gene, namely the carbamyl phosphate binding domain (encoded by the third exon) and the MspI restriction sites (CCGG) of the coding sequence (located in exons 2 and 7 respectively), as they contain mutation hot spots (CpG doublets). Using this procedure, we were able to identify three new mutant genotypes in OTC deficient children including one nonsense mutation (E 87 K, G 50 ter, G 162 R). Since genetic counselling for OTC deficiency is frequently difficult, molecular screening directed towards specific sites of the coding sequence could allow rapid detection of mutant genotypes and help solve diagnostic problems, especially when carrier status cannot be clarified easily.
鸟氨酸转氨甲酰酶（OTC）缺乏症是一种常见的X连锁尿素循环障碍疾病，可导致男性新生儿致命性高氨血症以及杂合子女性出现各种临床症状。为了提高我们对突变基因型的筛查效率，我们聚焦于OTC基因中具有功能或结构重要性的分子结构域，即氨甲酰磷酸结合结构域（由第三个外显子编码）和编码序列的MspI限制性位点（CCGG）（分别位于外显子2和7），因为它们包含突变热点（CpG双联体）。通过这个程序，我们能够在OTC缺乏症患儿中鉴定出三种新的突变基因型，包括一种无义突变（E 87 K、G 50 ter、G 162 R）。由于OTC缺乏症的遗传咨询常常很困难，针对编码序列特定位点的分子筛查能够快速检测出突变基因型，并有助于解决诊断问题，尤其是在携带者状态难以轻易明确的情况下。
