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目的探讨泰安地区苯丙氨酸羟化酶(phenylalanine hydroxylase,PAH)基因突变特点,为该地区苯丙酮尿症(phenylketonuria,PKU)的产前诊断、预防、治疗及人群干预措施的制定提供科学依据。方法采用下一代测序技术(NGS)对34例泰安地区PKU患儿及其父母的PAH基因的13个外显子及与外显子连接的上下游200 bp内含子进行测序分析。结果 34例患儿的68个PAH等位基因中共检出63个突变等位基因,突变检出率为92.65%(63/68),共检出28种突变类型。34例患儿均检测到突变位点,且均为杂合突变,其中1例患儿检测出3个突变位点,25例患儿检测到2个突变,8例患儿检测到1个突变。第7外显子为高频突变区,共检测到8种22个基因突变,相对突变频率为34.92%(22/63);第12外显子检测到4种10个基因突变,占总突变的15.87%(10/62)。共发现4种PAH基因新突变,p.H271L、p.D415N和p.M276K被确定为国内首次报道,p.E56D为国际上目前尚未报道过的PAH基因新突变。结论泰安地区PAH基因突变谱广,突变均为杂合突变,第7、12外显子为高频突变区。
Objective To investigate the characteristics of phenylalanine hydroxylase (PAH) gene mutations in Tai’an and provide a scientific basis for prenatal diagnosis, prevention, treatment and population intervention of phenylketonuria (PKU) in this area. . Methods The next generation sequencing (NGS) sequencing was performed on 13 exons of PAH gene and 200 bp upstream and downstream introns linked to exon in 34 children with PKU in Taian area and their parents. Results A total of 63 mutations alleles were detected in 68 PAH alleles of 34 children. The mutation detection rate was 92.65% (63/68). A total of 28 mutation types were detected. All 34 cases were detected mutation sites, and were heterozygous mutations, including 1 case detected 3 mutation sites, 25 cases detected 2 mutations in 8 cases of children detected a mutation . The 7th exon was a high-frequency mutation region. Totally 22 mutations were detected in 8 species, the relative mutation frequency was 34.92% (22/63). Four exon 10 mutations were detected in exon 12, accounting for the total number of mutations Of the 15.87% (10/62). Four novel PAH gene mutations were found, p.H271L, p.D415N and p.M276K were identified as the first reported in China, and p.E56D was a new PAH gene mutation not yet reported in the world. Conclusion The PAH gene mutation in Taian area is broad and the mutations are heterozygous mutations. The 7th and 12th exons are high frequency mutation areas.