RESUMO
Objective To determine the mutation spectrum of the PAH gene in PKU children in Ningxia, six exons of PAH gene were sequenced in each of the 30 phenylketonuria (PKU) children. Methods 30 children diagnosed as PKU by the neonatal sereening and/or GC/MS analysis in Ningxia were enrolled in this study. Meanwhile, 30 normal children were served as controls. The exons 3、5、6、7、11 and 12 of the PAH gene were ampliifed by polymerase chain reaction. The amplicons were analyzed by single strand conformation polymorphism and sequencing. Results Mutations were identiifed for 51 of 60 alleles in this study, representing a mutation detection rate of 85%. A total of 16 different causative mutations were detected, including 8 missense mutations (R 241 C、R 243 Q、R 252 Q、G 257 V、R 359 K、R 408 Q、R 413 P、Q 419 R), 3 splicing mutations (IVS 4-1 G?>?A、Y 204 C、IVS 7+2 T?>?A), 3 nonsense mutations (R 111 X、Q 160 X、Y 356 X), 1 synonymous mutation (V 399 V) and 1 deletion (N 183 del). R 243 Q ( 18 . 3%) had the highest frequency of PAH mutations, and then Y 204 C ( 11 . 7%)、IVS 4-1 G?>?A ( 10 . 0%)、R 111 X ( 6 . 7%) and IVS 7+2 T?>?A ( 6 . 7%). For the ifrst time in China, two novel mutations, deletion mutation N 183 del (C. 547-549 delGAA) in exon 6 and missense mutation R 359 K (C. 1078 G?>?A) in exon 11 , were identiifed in PKU children. Two silent mutations, V 245 V (C. 735 G?>?A) and Q 232 Q (C. 696 A?>?G), were observed in PKU children and the controls, but there were no signiifcant difference between them (P?>?0 . 05 ). Conclusions The most common mutations were missense and R 243 Q had the highest frequency of mutation. The identiifcation of 2 novel mutations expands the spectrum of Chinese PAH mutations.