Otc Gene Mutation And Clinical Analysis

Background Ornithine Carbamoyltransferase Deficiency is a common type of Urea Cycle Disorders,and is caused by Ornithine Carbamoyltransferase gene mutation,it is a X chromosome dominant inherited disease,it always firstly presents as encephalopathy or liver dysfunction.The human OTC gene is located on the short arm of the X chromosome within band Xp21.1,it includes 10 exons which encode ornithine carbamoyltransferase for urea cycle. Ornithine Carbamoyltransferase gene mutation result in dysfunction of Ornithine Carbamoyltransferase,it hinders the urea cycle,the ammonia can not become the atoxic urea,and there is hyperammonemia. Ornithine Carbamoyltransferase Deficiency's clinical manifestations are not specific,it is easy to misdiagnosis.But if diagnosis early and correctly and treatment effectively,it will save the patient and improve the prognosis. Ornithine Carbamoyltransferase gene mutations are scattered over the entire gene,and there are 341 mutations have been detected current update.Objective To explore the methods and importance of gene diagnosis for Ornithine Carbamoyltransferase Deficiency patient. The genotype and phenotype correlation in patients with Ornithine Carbamoyltransferase Deficiency was analyzed.Method Genomic DNA from peripheral blood was collected for genetic analysis in this patients. All exons and their flanking introns of OTC gene were screened by polymerase chain reaction combined with DNA direct sequencing in Ornithine Carbamoyltransferase Deficiency patients. Clinical manifestations and laboratory test results of the patients were summarized.Result Three of six patients were found with mutation.One patient was manifestation of liver and nervous system,a missense mutation of T262I in exon 8 of OTC gene,which was a homozygotic mutation,was identified,and his mother had the same mutation,which was a compound heterozygotic mutation in her peripheral blood but not any clinical symptoms. The other patient was presented as nervous system,a missense mutation of R277W in exon 8 of OTC gene,which was a homozygotic mutation,was identified,but his parents rejected to do gene analysis. Another patient was manifested of nervous system,a missense mutation of I172M in exon 5 of OTC gene,which was a homozygotic mutation was identified,and his mother had the same mutation,which was a compound heterozygotic mutation but not any clinical symptoms.The rest patients were not found OTC gene mutation.Conclusion Gene mutation analysis is a feasible way for diagnosing OTCD. I172M mutation patient present symptom early , T262I mutation and R277W mutation later. Gene mutation analysis will be important for asymptomatic and prenatal diagnosis and genetic counseling in the family.