福建泉州地区高苯丙氨酸血症相关基因变异特征的研究

Characteristics of gene variants among patients with hyperphenylalaninemia from Quanzhou region of Fujian province

目的构建福建泉州地区高苯丙氨酸血症(hyperphenylalaninemia,HPA)患者的基因变异谱.方法应用高通量测序技术对63例HPA患者的PAH、PTS、PCBD1、QDPR、SPR和GCH1基因进行变异分析.结果共检出PAH基因变异52例,PTS基因变异13例,其中PAH、PTS双基因变异2例.PAH基因的高频变异包括R53H(21.69%)、R241C(18.07%)、R243Q(12.05%)和EX6-96A>G(7.23%),集中于第7(32.53%)、第2(21.69%)、第6(9.64%)和第12(9.64%)外显子.L227M变异尚未见报道.PTS基因的高频变异包括N52S(35.00%)、P87S(25.00%)、IVS1291A>G(10.00%)和T67M(10.00%),集中于第2(35.00%)和第5(35.00%)外显子.结论泉州地区HPA患者的基因变异谱具有一定地域特异性.发现1种PAH基因新变异,即L227M.

Objective To explore the spectrum of genetic variants among patients with hyperphenylalaninemia(HPA)from Quanzhou area of Fujian province.Methods For 63 children affected with HPA,next generation sequencing was used to identify potential variants in PAH,PTS,PCBD1,QDPR,SPR and GCH1 genes.Results Fifty two variants underlying phenylalanine hydroxylase deficiency(PAHD)and 13 variants underlying 6 pyruvoyl tetrahydropterin synthase deficiency(PTPSD)were identified.Two patients carried variants of both PAH and PTS genes.The most common variants of the PAH gene were R53H(21.69%),R241C(18.07%),R243Q(12.05%)and EX6-96A>G(7.23%),which were mainly located in exons 7(32.53%),2(21.69%),6(9.64%)and 12(9.64%).The L227M variant of the PAH gene was unreported previously.N52S(35.00%),P87S(25.00%),IVS1-291A>G(10.00%)and T67M(10.00%)variants were the most common variants for the PTS gene and were mainly located in exons 2(35.00%)and 5(35.00%).Conclusion The variant spectrum underlying HPA in Quanzhou area showed a geographical specificity.A novel variant of the PAH gene(L227M)has been detected.