Mutation spectrum of PTS gene in patients with tetrahydrobiopterin deficiency from jiangxi province

Abstract

Background: Hyperphenylalaninemia (HPA) is the most common inborn error in amino acid metabolism. It can be primarily classified into phenylalanine hydroxylase (PAH) deficiency and tetrahydrobiopterin (BH4) deficiency. BH4 deficiency (BH4D) is caused by genetic defects in enzymes involved in the biosynthesis and regeneration of BH4. 6-pyruvoyl-tetrahydropterin synthase (PTPS/PTS), which is encoded by the PTS gene, participates in the biosynthesis of BH4. PTPS deficiency (PTPSD) is the major cause of BH4D. In this study, we investigated that the prevalence of BH4D in Jiangxi province was approximately 12.5 per 1,000,000 live births (69/5,541,627). Furthermore, the frequency of BH4D was estimated to be 28.8% (69/240) in the HPA population of Jiangxi. In this study, we aimed to characterize the mutational spectrum of the PTS gene in patients with PTPSD from Jiangxi province.Method: Newborn screening data of Jiangxi province from 1997 to 2021 were analyzed and 53 families with PTPSD were enrolled for the analysis of the PTS gene variants by Sanger sequencing.Results: 106 variants were identified in 106 alleles of 53 patients with PTPSD, including 13 types of variants reported previously, and two novel variants (c.164-36A>G and c.146_147insTG). The predominant variant was c.259C>T (47.2%), followed by c.84-291A>G (19.8%), c.155A>G (8.5%), c.286G>A (6.6%) and c.379C>T (4.7%).Conclusion: The results of this study can not only provide guidance for the molecular diagnosis and genetic counseling in cases of PTPS deficiency but also enrich the PTS mutation database.

Biochemical and molecular features of tetrahydrobiopterin deficiency in Fujian Province, southeastern China

“…In the present study, BH4D accounted for 15.87% of patients with HPA, which is similar to the proportion reported for Taiwan ( Niu et al, 2010 ). In addition, 29 out of the 30 (96.67%) patients with BH4D in our study had PTPSD, which is consistent with previous studies ( Ye et al, 2013 ; Han et al, 2015 ; Xie et al, 2022 ).…”

“…Only a few studies to date have investigated the prevalence of BH4D, with a global incidence of approximately 1 in 500,000 live births ( Blau et al, 2018 ); however, wide variation in the estimated prevalence has been reported depending on the geographical location and ethnic composition of the different provinces in China ( Wang et al, 2021 ; Xie et al, 2022 ). The prevalence of BH4D in the northern regions (4.1 per 1,000,000) of China is reportedly higher than that in the southern regions (1.6 per 1,000,000) ( Yuan et al, 2021 ).…”

“…The prevalence of BH4D in the northern regions (4.1 per 1,000,000) of China is reportedly higher than that in the southern regions (1.6 per 1,000,000) ( Yuan et al, 2021 ). The prevalence is up to 12.5 per 1,000,000 live births in Jiangxi Province, South China ( Xie et al, 2022 ), and estimated at 15.5 and 9.44 per 1,000,000 live births in Quanzhou city ( Lin et al, 2022 ) and Xianmen city ( Wang et al, 2019 ) of Fujian Province, respectively. In the present study, 30 patients with BH4D were identified among 3.2 million NBS results, representing an incidence of 9.36 per 1,000,000 live births in Fujian Province.…”

“…A previous study estimated the proportion of BH4D among patients with HPA in mainland China to be 8.55% ( Ye et al, 2009 ). However, significant regional differences in the proportion have also been observed, with a higher proportion in the southern region ( Xie et al, 2022 ) and a lower proportion in the northern region ( Han et al, 2015 ). In the present study, BH4D accounted for 15.87% of patients with HPA, which is similar to the proportion reported for Taiwan ( Niu et al, 2010 ).…”

Two Cases of 6-Pyruvoyl Tetrahydropterin Synthase Deficiency: Case Report and Literature Review

“…The c.84-3C > G variant is considered pathogenic in the ClinVar database (Variation ID: 553378), and was previously reported to be associated with as a severe form of PTPSD in Albania, Italy, and Iran [ 9 , 18 , 25 , 26 ].…”