[Analysis of GCH1 Gene Variant in a Consanguineous Chinese Pedigree Affected with Tetrahydrobiopterin Deficiency].

OBJECTIVE:To explore the genetic basis for a child featuring tetrahydrobiopterin deficiency and global developmental delay.METHODS:Clinical and laboratory examinations were carried out for the child. Genomic DNA of the patient was subjected to high-throughput sequencing to identify genetic variants associated with hyperphenylalaninemia. Candidate variants were verified by Sanger sequencing.RESULTS:The result of blood tandem mass spectrometry showed that the Phenylalanine in the blood was 642.7 μmol/l, and the ratio of Phenylalanine/Tyrosine was 5.42. Analysis of urinary pterin: neopterin 0.09 mmol/mol Cr, biopterin 0.04 mmol/mol Cr, biopterin% 77%, which suggested tetrahydrobiopterin deficiency. The parents of the proband were first cousins. DNA sequencing revealed that the proband has harbored homozygous c.353A>T variants in exon 2 of the GCH1 gene, for which his great grandmother, grandfather, mother, uncle, father and elder brother were heterozygous carriers with normal phenotype and no clinical symptoms associated with dopa responsive dystonia.CONCLUSION:The homozygous c.353A>T variant of the GCH1 gene probably underlay the tetrahydrobiopterin deficiency in this pedigree of consanguineous marriage.