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QDPR gene mutation and clinical follow-up in Chinese patients with dihydropteridine reductase deficiency
De-Yun Lu, Jun Ye, Lian-Shu Han, Wen-Juan Qiu, Hui-Wen Zhang, Jian-De Zhou, Pei-Zhong Bao, Ya-Fen Zhang, Xue-Fan Gu
Shanghai, China
Author Affiliations: Department of Pediatric Endocrinology and Genetic Metabolism and Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China (Lu DY, Ye J, Han LS, Qiu WJ, Zhang HW, Zhou JD, Bao PZ, Zhang YF, Gu XF)
Corresponding Author: Jun Ye, MD, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No.1665 Kong Jiang Road, Shanghai 200092, China (Tel: 86-21-25076455; Fax: 86-21-65791316; Email: yejun2314@163.com)
doi: 10.1007/s12519-014-0496-7
Background: This study aimed to investigate the mutation spectrum of the QDPR gene, to determine the effect of mutations on dihydropteridine reductase (DHPR) structure/function, to discuss the potential genotype-phenotype correlation, and to evaluate the clinical outcome of Chinese patients after treatment.
Methods: Nine DHPR-deficient patients were enrolled in this study and seven of them underwent neonatal screening. QDPR gene mutations were analyzed and confirmed by routine methods. The potential pathogenicity of missense variants was analyzed using Clustal X, PolyPhen program and Swiss-PDB Viewer 4.04_OSX software, respectively. The clinical outcomes of the patients were evaluated after long-term treatment.
Results: In 10 mutations of the 9 patients, 4 were novel mutations (G20V, V86D, G130S and A175R), 4 were reported by us previously, and 2 known mutations were identified. R221X was a hotspot mutation (27.7%) in our patients. Eight missense mutations probably had damage to protein. Six patients in this series were treated with a good control of phenylalanine level. The height and weight of the patients were normal at the age of 4 months to 7.5 years. Four patients, who underwent a neonatal screening and were treated early, showed a normal mental development. In 2 patients diagnosed late, neurological symptoms were significantly improved.
Conclusions: The mutation spectrum of the QDPR gene is different in the Chinese population. Most mutations are related to severe phenotype. The determination of DHPR activity should be performed in patients with hyperphenylalaninemia. DHPR-deficient patients who were treated below the age of 2 months may have a near normal mental development.
World J Pediatr 2014;10(3):219-226
Key words: dihydropteridine reductase;
hyperphenylalaninaemia;
tetrahydrobiopterin
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