期刊
HUMAN MUTATION
卷 27, 期 7, 页码 626-632出版社
WILEY
DOI: 10.1002/humu.20339
关键词
ornithine carbamoyl transferase; ornithine transcarbamylase; OTC; urea cycle; X-linked; hyperammonemia; private mutations
资金
- NCRR NIH HHS [M01-RR13297] Funding Source: Medline
- NIDDK NIH HHS [R01-DK47870] Funding Source: Medline
Ornithine transcarbamylase (OTC) deficiency is the most common inherited disorder of the urea cycle and is transmitted as an X-linked trait. Defects in the OTC gene cause a block in ureagenesis resulting in hyperammonemia, which can lead to brain damage and death. Three previous mutation updates for the OTC gene have been published, in 1993, 1995, and 2002. The most recent comprehensive update, in 2002, contained 244 mutations including 13 nondisease-causing mutations and polymorphisms. This current update reports 341 mutations, of which 93 have not been previously reported, and an additional 29 nondisease-causing mutations and polymorphisms. Out of the 341 mutations, 149 were associated with neonatal onset of hyperammonemia (within the first week of life), 70 were seen in male patients with later onset of hyperammonemia, and 121 were found in heterozygous females (one unknown). Along with the reported mutations, residual enzyme activities and other pertinent clinical information are included whenever available. Most mutations in the OTC gene are specific to a particular family (private mutations). They are distributed throughout the gene, with a significant paucity of mutations in the 32 first codons encoding the leader peptide (exon 1 and the beginning of exon 2). Almost all mutations in consensus splice sites confer a neonatal onset phenotype. Using the current molecular screening methods, mutations are found in about 80% of the patients. The remaining patients may have mutations in regulatory domains or mutations deep in the introns, which constitute 98.5% of the genomic sequence. In addition, a phenocopy of OTC deficiency caused by mutations in another unknown gene cannot be excluded. Hum Mutat 27 (7), 626-63 2, 2006. Published 2006 Wiley,Liss, Inc.(dagger).
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