Abstract:

Objective: To investigate the gene mutations of seven families suspected with urea cycle disorders (UCD), and to perform prenatal diagnosis for two reproductive families. Methods: Target sequence capture combined with high-throughput next-generation sequencing, and Sanger sequencing/LD-PCR/MLPA (multiplex ligation-dependent probe amplification) technologies were used to investigate the gene mutations for seven families suspected with UCD. After the genotypes of the pedigrees were identified, two amniotic fluid samples from high-risk pregnant women were used for prenatal genetic diagnosis. Results: The diagnosis of UCD was confirmed in seven suspected families. Among of them, four patients were diagnosed as the neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and one of them was coexist with spinal muscular atrophy (SMA). One patient was diagnosed with citrullinaemia typeⅠ(CTLN1). And two patients were diagnosed with ornithine transcarbamylase deficiency (OTCD). Prenatal genetic diagnosis of two families show that one fetus had a mutation at a heterozygous mutation of SLC25A13 with paternal; and another one was a proband with normal OTC gene. Conclusions: Genetic diagnostic can make accurate and effective diagnosis of UCD. However, some families with suspected UCD could have normal OTC gene. The prenatal genetic diagnosis combined with OTC gene testing can prevent the rebirth defects in high-risk families.

Key words: Urea cycle disorders,inborn, Citrullinemia, Ornithine carbamoyltransferase deficiency disease, DNA mutational analysis, Prenatal diagnosis, Neonatal intrahepatic cholestasis caused by citrin deficiency