Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients
| Autor: | Yushan Huang, Jun Zhu, Lijie Ding, Jian Wang, Ping Yu, Huanming Yang, Bin Rao, Ying Deng, Yixiong Guo, Zhen Liu, Jian Guo, Fang Chen, Nana Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Male medicine.medical_specialty China Endocrinology Diabetes and Metabolism Genetic counseling Prenatal diagnosis medicine.disease_cause Peroxisomal Targeting Signals 03 medical and health sciences Endocrinology Hyperphenylalaninemia Neonatal Screening Asian People Dihydropteridine Reductase Internal medicine Molecular genetics Phenylketonurias Prenatal Diagnosis medicine Humans GTP Cyclohydrolase Tetrahydrobiopterin deficiency Hydro-Lyases Mutation business.industry Incidence (epidemiology) Infant Newborn Infant medicine.disease Prognosis QDPR 030104 developmental biology Child Preschool Pediatrics Perinatology and Child Health Female business Biomarkers Follow-Up Studies |
| Zdroj: | Journal of pediatric endocrinologymetabolism : JPEMReferences. 31(8) |
| ISSN: | 2191-0251 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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