Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients
-
Nana Li
,
Fang Chen
and
Zhen Liu
Abstract
Background
The overall incidence of hyperphenylalaninemia (HPA) in China is 1:11,763, with tetrahydrobiopterin (BH4) deficiency accounting for 8.55% of patients with HPA in the mainland. Much progress has been made in the diagnosis and treatment of BH4 deficiency with the introduction of neonatal screening in China. However, the screening rate is still low and screening is not universally available.
Methods
A total of 44 BH4-deficient patients were enrolled in this study, of which 39 were diagnosed with BH4 deficiency, while the remaining five showed typical characteristics of BH4 deficiency at a later period. The entire coding regions and adjacent intronic regions of GCH1, PTS, PCBD1 and QDPR genes were analyzed using target sequencing.
Results
Nineteen (n=19) different mutations in the PTS gene including four novel mutations and one mutation in QDPR were identified. p.P87S, p.D96N, IVS1-291A>G, p.N52S, p.K91R, p.V56M, p.T106M and p.F40GfsX53 in PTS were the prevalent mutations with ≥3% relative frequency. The mutation p.R221X in the QDPR gene was found with relatively lower frequencies (2.27%). The remaining 12 mutations in PTS were found at relative frequencies of 1.14%.
Conclusions
The results could be of value for genetic counseling and prenatal diagnosis in the patients’ families and for the molecular diagnosis of BH4 deficiencies. Furthermore, four novel mutations expand and improve the PTS mutation database.
Acknowledgments
We thank all the children and their parents for participating in this study and for providing personal information. We thank the staff at the newborn screening centers involved in the project process of recruitment and data collection.
Author contributions: Zhen Liu, Fang Chen and Jian Guo developed the study design, conducted the study and drafted the manuscript. Nana Li, Ping Yu, Ying Deng and Yixiong Guo assisted in organizing and collecting the samples. Lijie Ding and Yushan Huang carried out genetic data acquisition and interpretation. Nana Li, Ping Yu and Bin Rao analyzed the data. Jun Zhu, Huanming Yang and Jian Wang participated in reviewing, editing and revising the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by the National Natural Science Foundation of China (Nos. 81573165, 81602865), the National Science & Technology basic work Project of the Ministry of Science and Technology of China (grant ID: 2014FY 110700), and the National “Twelfth Five-Year” Plan for Science & Technology Support of China (grant ID: 2014BAI06B01), the Program for Changjiang Scholars and Innovative Research Team in University (grant ID: IRT0935).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2018-0037).
©2018 Walter de Gruyter GmbH, Berlin/Boston
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Articles in the same Issue
- Frontmatter
- Original Articles
- Urinary bisphenol-A levels in children with type 1 diabetes mellitus
- The relationship between metabolic syndrome, cytokines and physical activity in obese youth with and without Prader-Willi syndrome
- Association of anthropometric measures and cardio-metabolic risk factors in normal-weight children and adolescents: the CASPIAN-V study
- The effect of obesity and insulin resistance on macular choroidal thickness in a pediatric population as assessed by enhanced depth imaging optical coherence tomography
- Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation
- Long-term thyroid disorders in pediatric survivors of hematopoietic stem cell transplantation after chemotherapy-only conditioning
- Screening for autoimmune thyroiditis and celiac disease in minority children with type 1 diabetes
- Resistance exercise alone improves muscle strength in growth hormone deficient males in the transition phase
- Sequential measurements of IGF-I serum concentrations in adolescents with Laron syndrome treated with recombinant human IGF-I (rhIGF-I)
- Symptomatic Rathke cleft cyst in paediatric patients – clinical presentations, surgical treatment and postoperative outcomes – an analysis of 38 cases
- Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients
- Single center experience of biotinidase deficiency: 259 patients and six novel mutations
- Next-generation sequencing as a second-tier diagnostic test for newborn screening
- Case Reports
- Thyroid storm after choking
- Three new Brazilian cases of 17α-hydroxylase deficiency: clinical, molecular, hormonal, and treatment features
- Diazoxide toxicity in a child with persistent hyperinsulinemic hypoglycemia of infancy: mixed hyperglycemic hyperosmolar coma and ketoacidosis
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