Mutation spectrum and new mutation of phenylalanine hydroxylase gene in Guangxi region

Objective To investigate the characteristics of the phenylalanine hydroxylase(PAH) gene mutations in patients with phenylketonuria(PKU) in Guangxi region, in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty-seven children diagnosed as PKU in the Maternal and Children′s Hospital of Guangxi Zhuang Autonomous Region were enrolled in the study between January 2009 and December 2017. Venous blood was collected and the PAH gene sequence was determined by Sanger sequencing after amplification with the polymerase chain reaction technique. The new gene mutations were defined based on the national and international literature review and databases.Meanwhile, 100 healthy individuals were selected as the control group for gene sequencing to confirm whether the mutation was a new one. Results Thirty-seven cases of PKU were detected for 68 mutations, with the detection rate being 91.89% (68/74). Six mutations were identified in exon 7, which accounted for 31.08% of all, exon 12(18.92%), exon 8(10.81%) and exon 6 (10.81%) followed.A total of 25 different mutations were identified which including 14 missense mutations(56.00%), 7 nonsense mutations(28.00%), 3 splicing junction mutations(12.00%), and 1 deletion mutation(4.00%). The most common mutations included c. 1223G>A(p.R408Q), c.728G>A(p.R243Q) and c. 721C>T(p.R241C), accounting for 14.86%, 13.51%, and 10.81%, respectively.After querying international databases, including PAH mutation database and Human Gene Mutation Database and forecasting software, three kinds of mutations c. 314C> T (p.T105I), c.583A> G (p.K195E), c .851G> A(p.C284Y) were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified.And 3 kinds of mutations have been identified.This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region. Key words: Phenylketonuria; Phenylalanine hydroxylase; Gene mutation