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J Pediatr Endocrinol Metab. 2018 Aug 28;31(8):911-916. doi: 10.1515/jpem-2018-0037.

Molecular genetics of tetrahydrobiopterin deficiency in Chinese patients.

Li N1,2, Yu P1,2, Rao B3,4, Deng Y1, Guo Y1, Huang Y3,4, Ding L3,4, Zhu J1,2, Yang H3,5, Wang J3,5, Guo J6,7,8, Chen F6,7,8, Liu Z9,10.

Author information

1
National Center for Birth Defects Monitoring, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
2
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, P.R. China.
3
BGI-Shenzhen, Shenzhen, P.R. China.
4
China National GeneBank, BGI-Shenzhen, Shenzhen, P.R. China.
5
James D. Watson Institute of Genome Sciences, Hangzhou, P.R. China.
6
BGI-Shenzhen, Building 11, Beishan Industrial Zone, Yantian, Shenzhen, Guangdong, P.R. China, Phone: 86-15914038192.
7
BGI-Shenzhen, Building 11, Beishan Industrial Zone, Yantian, Shenzhen, Guangdong, P.R. China, Phone: 86-13428735579.
8
China National GeneBank, BGI-Shenzhen, Shenzhen, Guangdong, P.R. China.
9
National Center for Birth Defects Monitoring, West China Second University Hospital, Sichuan University, 20, Section 3, Ren Min South Road, Chengdu, Sichuan, P.R. China, Phone: 86-028-85502490, Fax: 86-028-85501386.
10
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, P.R. China.

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.

KEYWORDS:

6-pyruvoyltetrahydropterin synthase; mutation; quinoid dihydropteridine reductase; tetrahydrobiopterin deficiencies

PMID:
30001213
DOI:
10.1515/jpem-2018-0037
[Indexed for MEDLINE]

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