Study on the mutations of phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi province
Study on the mutations of phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi province
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DOI：
10.3760/cma.j.issn.1003-9406.2011.04.007
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发表时间：
2011-08-10
期刊：
影响因子：
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通讯作者：
Zhou Yong-an
中科院分区：
文献类型：
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作者：
Gao Wei-hua;Zhang Quan-bin;Zhou Yong-an
目的研究山西人群苯丙氨酸羟基酶基因(PAH)第3、6、7、11、12外显子的突变情况。方法采用聚合酶链式反应-DNA测序法，对59例苯丙酮尿症(PKU)患者和100例健康儿童的PAT-I基因外显子3、6、7、11、12及其侧翼序列进行突变检测。结果通过序列分析，在患儿和健康儿童中均检测到Q232Q(CAA->；CAG)、V245V(GTG->；GTA)和L385L(CTG->；CTC)3个单核苷酸多态(SNP)，其中PAH基因的696、735和1155位点的频率高达96。2%，76%。患者分别为1%和7.6%，97。0%，77%。健康对照组分别为3%和8.3%。此外，72个不同的突变占61个。仅在患者中发现0%的突变等位基因。在外显子3中，R111X、H64>；TfsX9和S70 del分别占5.1%、0.8%和0。外显子6的EX6-96A和GT；G占10.2%。在第7外显子中，R243Q的发病率最高，占12.7%，其次是IVs7+2 T>；A(5.1%)和T278I(2.5%)，发病率最低的是G247V、R252Q、L255S、R261Q和E280K。分别为8%。在外显子11中发现Y356X(5.9%)和V399V(5.1%)，在外显子12中发现R413P和A434D分别占5.9%和2.5%。在16种不同的突变中，共有9个错义突变、3个剪接点突变、2个无义突变和2个缺失突变。结论明确了山西地区PKU人群PAH基因第3、6、7、11、12外显子的突变特点和分布，提示EX6-96A&Gt；G和R243Q是山西地区PKU人群PAH基因突变的热点。
Objective To study the mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase gene (PAH) in Shanxi population. Methods The mutations in exons 3, 6, 7, 11 and 12 and flanking sequences of PAT-I gene were detected by PCR-DNA sequencing, in 59 patients with phynelketonuria(PKU) and 100 healthy children from Shanxi province. Results By sequence analysis, three single nucleotide polymorphism (SNP) Q232Q (CAA -> CAG),V245V (GTG -> GTA) and L385L (CTG -> CTC) were detected in both the patients and healthy children, with the frequencies of nt 696, 735 and 1155 of the PAH cDNA up to 96. 2%, 76. 1 % and 7. 6% in patients respectively,and 97. 0%,77. 3% and 8. 3% respectively in the healthy controls. In addition, 72 different mutations accounting for 61. 0% of mutant alleles were identified in the patients only. In exon 3, R111X, H64 > TfsX9 and S70 del were found accounting for 5. 1 %,0. 8% and 0. 8%; EX6-96A>G in exon 6 was found accounting for 10. 2%. In exon 7, R243Q was the highest incidence accounting for 12. 7%, followed by Ivs7 + 2 T>A (5. 1%) and T278I (2. 5%); the lowest incidences were G247V, R252Q, L255S, R261Q and E280K accounting for 0. 8 %, respectively. In exon 11, Y356X (5. 9%) and V399V (5. 1%) were found; in exon 12, R413P and A434D were found accounting for 5. 9% and 2. 5%. In total, 9 missense mutations, 3 splice site mutations, 2 nonsense mutations and 2 deletions were included in 16 kinds of different mutations. Conclusion The mutation characteristics and distribution in exons 3,6,7,11 and 12 of the PAH gene have been identified, and it suggested that the EX6-96A>G and R243Q were the hot spots of PAH gene mutations in Shanxi PKU population.