Dataset Information

Gene Mutation Analysis and Prenatal Diagnosis of the Ornithine Transcarbamylase (OTC) Gene in Two Families with Ornithine Transcarbamylase Deficiency.

ABSTRACT: BACKGROUND The aim of this study was to perform gene detection in 2 clinical cases of highly suspected ornithine transcarbamylase deficiency (OTCD) pediatric patients by first-generation sequencing technology in order to confirm the pathogenic genetic factors of their families and allow the families to undergo genetic counselling and prenatal diagnosis. MATERIAL AND METHODS The peripheral DNA samples of 2 children with highly suspected OTCD (the probands) and their parents were collected. DNA fragments corresponding to exons 1-10 of the OTC gene from the samples were amplified using polymerase chain reaction (PCR), and then subjected to Sanger sequencing to confirm the pathogenic mutation sites. RESULTS The probands were both confirmed to have OTCD. The proband in Family 1 was a male carrying a c.867+1G>C mutation at a splice site within the OTC gene. The gene detection results of amniotic fluid cells at 16 weeks of pregnancy showed that the fetus was a male who also carried the c.867+1G>C mutation. The proband in Family 2 was a male carrying a c.782T>C(p. I261T) mutation in the OTC gene. The gene detection results of amniotic fluid cells at 18 weeks showed that the fetus was a male without pathogenic mutations in the OTC gene. The gene detection results of peripheral blood from the fetus after birth were consistent with those obtained from amniotic fluid cells. CONCLUSIONS Pediatric children who are clinically suspected of OTCD can receive a definitive diagnosis through OTC gene detection.

SUBMITTER: Li S

PROVIDER: S-EPMC6354644 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Gene Mutation Analysis and Prenatal Diagnosis of the Ornithine Transcarbamylase (OTC) Gene in Two Families with Ornithine Transcarbamylase Deficiency.

Li Sitao S Cai Yao Y Shi Congcong C Liu Mengxian M Liu Bingqing B Lin Lin L Xiao Xin X Hao Hu H

Medical science monitor : international medical journal of experimental and clinical research 20181018

BACKGROUND The aim of this study was to perform gene detection in 2 clinical cases of highly suspected ornithine transcarbamylase deficiency (OTCD) pediatric patients by first-generation sequencing technology in order to confirm the pathogenic genetic factors of their families and allow the families to undergo genetic counselling and prenatal diagnosis. MATERIAL AND METHODS The peripheral DNA samples of 2 children with highly suspected OTCD (the probands) and their parents were collected. DNA fr ...[more]

PMID: 30333473

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Project description:Background: Ornithine transcarbamylase deficiency (OTCD) is an X- linked recessive disorder and the most common error of the urea cycle, caused by the mutations in the OTC gene. Due to X-inactivation, 15-20% of female carriers present symptoms of OTCD at late onset. Early diagnosis of OTCD by molecular analysis in females is highly desirable. The aim of the study was to identify the mutations in two unrelated Vietnamese girls suspected with OTCD and the carriers in their families for definitive diagnosis and proper counseling. Case Presentation: Two patients presented with an acute encephalopathy at the first admission. Biochemical tests revealed hyperammonemia, hyperlactatemia, elevated glutamine level, elevated transaminase, elevated urinary orotic and uracil acid levels, and disorder of prothrombin time. Brain magnetic resonance imaging indicated cerebral edema. Based on the clinical and laboratory results, the two patients were diagnosed with urea cycle disorders. Therefore, the two patients were managed by stopping feeding, with infused glucose, l-carnitine, l-arginine, and sodium benzoate, and with hemofiltration. The two patients were alert and recovered with normal blood ammonia levels after 72 h of treatment. The family history of patient 1 showed that her brother died at 4 days of age due to a coma and dyspnea, while her parents were asymptomatic. Variable phenotypes were observed in three generations of the patient 2's family, including asymptomatic (mother), affected female adults dying at the first symptom (grandmother and aunt), and affected males dying in the first week of life (uncle, cousin, and siblings). Whole-exome sequencing showed two mutations in the OTC gene, including one novel missense mutation, c.365A>T, in the patient 1 and one previously reported splicing mutation, c.717+1G>A, in the patient 2. The two mutations are evaluated as likely pathogenic and pathogenic, respectively, according to the recommendations of the American College of Medical Genetics and Genomics (ACMG). Genetic analyses in the families indicated the mothers were heterozygous. Conclusion: Clinical, biochemical, and molecular findings accurately diagnosed the two patients with late-onset OTCD. Our results explained the genetic causes and proposed the risk in the patients' families, which could be useful for genetic counseling and monitoring in prenatal diagnosis.

Dataset Information

Gene Mutation Analysis and Prenatal Diagnosis of the Ornithine Transcarbamylase (OTC) Gene in Two Families with Ornithine Transcarbamylase Deficiency.

Publications

Gene Mutation Analysis and Prenatal Diagnosis of the Ornithine Transcarbamylase (OTC) Gene in Two Families with Ornithine Transcarbamylase Deficiency.

Similar Datasets

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