中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2010年
1期
7-12
,共6页
宋力%党利亨%孟英韬%付伯津
宋力%黨利亨%孟英韜%付伯津
송력%당리형%맹영도%부백진
苯丙酮尿症%苯丙氨酸羟化酶%突变谱
苯丙酮尿癥%苯丙氨痠羥化酶%突變譜
분병동뇨증%분병안산간화매%돌변보
phenylketonuria%phenylalanine hydroxylase%mutation spectrum
目的 分析天津地区人苯丙氨酸羟化酶(phenylalanine hydroxylase gene,PAH)基因突变谱,明确本地区该基因突变类型和特点,为遗传咨询和产前基因诊断提供科学依据.方法 用聚合酶链反应-单链构象多态、变性高效液相色谱法和DNA测序法对天津及河北等地99例已确诊各种类型苯丙酮尿症患儿基因组DNA进行PAH全基因13个外显子分析.结果 全基因共检出41种突变,含错义突变22种、无义突变7种、剪接位点突变9种和缺失突变3种.其中新突变6种(IVS3nt+1g→a、A165D、Q301X、G344D、P362L和R413G).198个PAH等位基因突变总检出率为93.94%.结论 天津及周边地区PAH基因突变谱广、遗传异质性高,一些常见突变的发生频率与以往报道的地域分布略不同.
目的 分析天津地區人苯丙氨痠羥化酶(phenylalanine hydroxylase gene,PAH)基因突變譜,明確本地區該基因突變類型和特點,為遺傳咨詢和產前基因診斷提供科學依據.方法 用聚閤酶鏈反應-單鏈構象多態、變性高效液相色譜法和DNA測序法對天津及河北等地99例已確診各種類型苯丙酮尿癥患兒基因組DNA進行PAH全基因13箇外顯子分析.結果 全基因共檢齣41種突變,含錯義突變22種、無義突變7種、剪接位點突變9種和缺失突變3種.其中新突變6種(IVS3nt+1g→a、A165D、Q301X、G344D、P362L和R413G).198箇PAH等位基因突變總檢齣率為93.94%.結論 天津及週邊地區PAH基因突變譜廣、遺傳異質性高,一些常見突變的髮生頻率與以往報道的地域分佈略不同.
목적 분석천진지구인분병안산간화매(phenylalanine hydroxylase gene,PAH)기인돌변보,명학본지구해기인돌변류형화특점,위유전자순화산전기인진단제공과학의거.방법 용취합매련반응-단련구상다태、변성고효액상색보법화DNA측서법대천진급하북등지99례이학진각충류형분병동뇨증환인기인조DNA진행PAH전기인13개외현자분석.결과 전기인공검출41충돌변,함착의돌변22충、무의돌변7충、전접위점돌변9충화결실돌변3충.기중신돌변6충(IVS3nt+1g→a、A165D、Q301X、G344D、P362L화R413G).198개PAH등위기인돌변총검출솔위93.94%.결론 천진급주변지구PAH기인돌변보엄、유전이질성고,일사상견돌변적발생빈솔여이왕보도적지역분포략불동.
Objective To investigate the characteristics of the phenylalanine hydroxylase (PAH)gene mutations in patients with phenylketonuria (PKU) in Tianjin and surrounding area, in order to provide basic information for genetic counseling and prenatal gene diagnosis. Methods All of the 13 exons and flanking introns of the PAH gene from 99 patients with PKU were amplified by polymerase chain reaction and analyzed by single strand conformation polymorphism (SSCP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Results Mutations were found in all exons or flanking introns of the PAH gene except for exons 9 and 13. A total of 41 different mutations were identified which corresponded to 93. 94% (186/198) of the PAH alleles, including 22 missense mutations (53. 6%), 7nonsense mutations (17.1%), 9 splicing junction mutations(22.0%), and 3 deletion mutations (7.3%).Six novel mutations (IVS3nt+1g→a, A165D, Q301X, G344D, P362L and R413G) were identified and another 6 mutations (S16fsdelCT, R71H, IVS5nt+1g→a, G239S, R243X and R261X) were reported in Chinese population for the first time according to the databases from http://www. pahdb. mcgill. ca. The most common mutations included 243Q (36/198,18.18%), V399V (22/198, 11. 1%), R111X (19/198,9.6%), E6nt-96A→g (18/198, 9.1%), R413P (15/198, 7.6%) and Y356X (13/198, 6. 6%). In addition, 4 silent mutations (except V399V) in exons and 8 variations in introns were found in this study.The IVS1nt + 40t→g and IVS10nt-31g→a were confirmed as novel variations by international PAH databases and IVS5nt-54g→a was the first report in China. Conclusion The frequencies of six common mutations were close to that in Beijing area of China, but it was different in sequence. The extensive mutation spectrum of the PAH gene showed higher heterogeneity in Tianjin and surrounding areas of Northern China comparing with other reports. According to this report, exons 7 and 11 are the hot spots and should be detected first for PAH gene quick diagnosis in this area, then comes exons 3, 6 and 12, and finally exons 5, 10 and others.
