ABSTRACT
Objective To analyze the mutation distribution of phenylalanine hydroxylase(PAH)gene in pa-tients with phenylketonuria(PKU)in Ningxia,and understand the hot spots and regions of PAH gene. Methods First-ly,6 hot mutation exons including 3,5,6,7,11,12 and their surrounding introns of the PAH gene in 30 patients with PKU in Ningxia were directly sequenced. And then the last 7 exons of 1,2,4,8,9,10,13 were sequenced for the patients in which 2 mutant alleles were not characterized. Multiplex ligation - dependent probe amplification (MLPA)was performed for the identification of uncharacterized mutant alleles after PAH sequence analysis of patients with PKU. Results Among 60 alleles,there were 58 mutant alleles(96. 7% ). Forty - six(81. 6% )mutant alleles were found in the exons 3,5,6,7,11,12. A total of 23 various mutations were detected,including missense(n = 9), splicing(n = 9),nonsense(n = 2),small deletion(n = 2)and large deletion(n = 1). The most common mutations were R243Q(18. 3% ),IVS4 - 1G ﹥ A(11. 7% )and R111X(11. 7% ). Among them,a novel mutation N393del was detec-ted in exon 11. MLPA identified a large deletion(c. - 1932 + 3402del)in 3 patients,1 of them was homoallelic muta-tion,and the others were heteroallelic mutation. Conclusions There are obvious hotspots and hot spot areas of PAH gene in PKU patients in Ningxia. There is a large deletion mutation in PKU patients in Ningxia. The MLPA is an effec-tive assay to detect large deletion in PAH gene.