Analysis of GCH1 gene variant in a consanguineous Chinese pedigree affected with tetrahydrobiopterin deficiency
10.3760/cma.j.cn511374-20201206-00851
- VernacularTitle:近亲婚配所致四氢生物喋呤缺乏症家系的 GCH1基因变异分析
- Author:
Xiaole LI
1
;
Dengna ZHU
;
Su′na LIU
;
Chenlu JIA
;
Yaqing GUO
;
Linlin ZHANG
;
Mingmei WANG
;
Dehua ZHAO
Author Information
1. 郑州大学第三附属医院新生儿疾病筛查科，郑州 450052
- Keywords:
Tetrahydrobiopterin deficiency;
GCH1 gene;
Consanguineous marriage
- From:
Chinese Journal of Medical Genetics
2022;39(7):713-717
- CountryChina
- Language:Chinese
-
Abstract:
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.
