广州地区61例苯丙酮尿症患儿苯丙氨酸羟化酶基因突变分析-妇产科学专业论文.docxVIP

广州医科大学硕士学位论文 广州医科大学硕士学位论文 广州地区 61 例苯丙酮尿症患儿苯丙氨酸羟化酶基因突变分析 PAGE PAGE 10 2．Sequence analysis: the sequence results were analyzed by Chromas, sequence alignments were performed by Clustalx. The mutations detected were named referring to PAH locus database （ HYPERLINK http://www.pahdb.mcgil1.ca/ http://www.pahdb.mcgil1.ca）. 3．Statistical analysis: Two independent sample t – test was used,with test level a = 0.05, by SPSS13.0 statistical software. Results 1．In this study, we identified fifty-three different mutations in total, including thirty-five missense mutations, six nonsense mutations, five splice mutations, three deletion mutations, one silent mutations, one silent/spice mutation and one deletion/ insertion mutation. 2．The frequency of mutations in exon 7 is the hightest (35.8%).The most common mutations in this study were R243Q,R241C and R243Q,with frequencies 9.84%,9.02% and 5.74% respectively. 3．In the sixty-one patients, two mutations were identified in each of the forty-nine patients, one mutations were identified in eight patients, three pathogenic mutations in one patients and no pathogenic mutations were identified in three patients. 4．Twelve novel mutations were identified in this study : S446G、P392I、F331S、 L293S、H285R、Y154X、Q172H、F161fsX24、A246T、R158G Y166X、H107R. 5．Two family results The one family fetus were(twins) diagnosed as a carrier,which inherited from the mother,s PAH gene mutation; Another other family both of the parents were PAH gene carriers , the proband and his brother by sequencing detection was PKU patients which inherited from their parents PAH gene mutation. Conclusion 1．We obtained the PAH mutation spectrum in Guangzhou . A total of 53 different mutations were identified in this study, of which R243Q 、 R241C 、 EX6-96AG were the hotspots mutations,with frequency9.84%,9.02% and 5.74% respectively. 2．The mutation frequency in exon 7 is the hightest. 3．Twelve novel mutations were detected