1例17α-羟化酶/17,20-碳链裂解酶缺陷症患者临床分析和基因检测
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摘要
目的对1例17α-羟化酶/17,20-碳链裂解酶缺陷症(17α-hydroxylase/17,20-lyase deficiency,17OHD)患者进行基因检测。方法 1例17OHD患者,抽提其外周血DNA,采用PCR扩增CYP17A1基因外显子及外显子与内含子交接区域,采用直接测序法对PCR产物进行序列检测和分析。结果该例患者CYP17A1基因上检测到纯合突变c.985-987delinsAA(p.Y329KfsX89),该突变生成包含417个氨基酸的截短蛋白。结论该例患者17OHD是由纯合突变c.985-987delinsAA(p.Y329KfsX89)所致。
Objective To detect the mutation of CYP17A1 gene of a patient with 17α-hydroxylase/17,20-lyase deficiency(17OHD).Methods The genomic DNA of this patient was obtained from peripheral blood leukocytes.The exons and exon-intron boundaries of the CYP17A1 gene were PCR-amplified,and the PCR products were directly sequenced to screen mutations.Results A homozygous mutation c.985-987 delins AA(p.Y329KfsX89)was found in this patient,including the truncated proteins of 417 amine acids.Conclusion A homozygous mutation c.985-987 delins AA(p.Y329KfsX89)causes 17 OHD in this patient.
Objective To detect the mutation of CYP17A1 gene of a patient with 17α-hydroxylase/17,20-lyase deficiency(17OHD).Methods The genomic DNA of this patient was obtained from peripheral blood leukocytes.The exons and exon-intron boundaries of the CYP17A1 gene were PCR-amplified,and the PCR products were directly sequenced to screen mutations.Results A homozygous mutation c.985-987 delins AA(p.Y329KfsX89)was found in this patient,including the truncated proteins of 417 amine acids.Conclusion A homozygous mutation c.985-987 delins AA(p.Y329KfsX89)causes 17 OHD in this patient.
引文
[1]Keskin M,Ugurlu AK,Savas-Erdeve S,et al.17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A)mutation in CYP17A1gene[J].J Pediatr Endocrinol Metab,2015,28(7/8):919-921.
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[7]吴庆华,信艳萍,张毅,等.17α-羟化酶/17,20-碳链裂解酶缺陷症的诊断及治疗效果探讨[J].中华妇产科杂志,2015,50(2):140-143.
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[10]Han B,Liu W,Zuo CL,et al.Indentifying a novel mutation of CYP17A1gene from five Chinese 17α-hydroxylase/17,20-lyase deficiency patients[J].Gene,2013,516(2):345-350.
[11]Yanase T,Simpson ER,Waterman MR.17 Alphahydroxylase/17,20-lyase deficiency:from clinical investigation to molecular definition[J].Endocr Rev,1991,12(1):91-108.
[12]Yamakita N,Murase H,Yasuda K,et al.Possible hyperaldosteronism and discrepancy in enzyme activity deficiency in adrenal and gonadal glands in Japanese patients with 17alpha-hydroxylase deficiency[J].Endocrinol Jpn,1989,36(4):515-536.
[13]Athanasoulia AP,Auer M,Riepe FG,et al.Rare missense P450c17(CYP17A1)mutation in exon 1as a cause of 46,XY disorder of sexual development:implications of breast tissue unresponsiveness despite adequate estradiol substitution[J].Sex Dev,2013,7(4):212-215.
[14]Qiao J,Han B,Liu BL,et al.A unique exonic splicing mutation in the CYP17A1 gene as the cause for steroid 17{alpha}-hydroxylase deficiency[J].Eur J Endocrinol,2011,164(4):627-633.
[15]Turkkahraman D,Guran T,Ivison H,et al.Indentification of a novel large CYP17A1deletion by MLPA analysis in a family with classic 17α-hydroxylase deficiency[J].Sex Dev,2015,9(2):91-97.
[16]Zhang M,Sun S,Liu Y,et al.New,recurrent,and prevalent mutations:clinical and molecular characterization of 26Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency[J].J Steroid Biochem Mol Biol,2015,150(6):11-16.
[17]郑瑞芝,赵志刚,汪艳芳,等.先天性肾上腺皮质增生症6例临床分析[J].中华实用诊断与治疗杂志,2010,24(4):399-402.
[2]杨科,张冰,崔淑娴,等.一例17α-羟化酶/17,20-碳链裂解酶缺陷症患儿的CYP17A1基因突变分析[J].中华医学遗传学杂志,2013,30(4):439-442.
[3]Xue LQ,Han B,Chen LB,et al.Indentification of a novel mutation in CYP17A1gene[J].Transl Res,2013,161(1):44-49.
[4]Biglieri EG,Herron MA,Brust N,et al.17-Hydroxylation deficiency in man[J].J Clin Invest,1996,45(12):1946-1954.
[5]王莉,王涛,康冰,等.应用PCR技术对4例DMD家系进行产前基因诊断[J].中华实用诊断与治疗杂志,2010,24(2):133-135.
[6]林纬,郭秋璇,陈刚,等.17α-羟化酶/17,20-碳链裂解酶缺陷症的临诊应对[J].中华内分泌代谢杂志,2014,30(12):1120-1124.
[7]吴庆华,信艳萍,张毅,等.17α-羟化酶/17,20-碳链裂解酶缺陷症的诊断及治疗效果探讨[J].中华妇产科杂志,2015,50(2):140-143.
[8]Tian Q,Yao F,Zhang Y,et al.Molecular study of five Chinese patients with 46XX partial 17a-hydroxylase/17,20-lyase deficiency[J].Gynecol Endocrinol,2012,28(3):234-238.
[9]周迪禹,邱文娟,徐卯升,等.婴儿期诊断的一例孤立性17,20碳链裂解酶缺乏症临床和基因分析[J].中华儿科杂志,2014,54(8):619-622.
[10]Han B,Liu W,Zuo CL,et al.Indentifying a novel mutation of CYP17A1gene from five Chinese 17α-hydroxylase/17,20-lyase deficiency patients[J].Gene,2013,516(2):345-350.
[11]Yanase T,Simpson ER,Waterman MR.17 Alphahydroxylase/17,20-lyase deficiency:from clinical investigation to molecular definition[J].Endocr Rev,1991,12(1):91-108.
[12]Yamakita N,Murase H,Yasuda K,et al.Possible hyperaldosteronism and discrepancy in enzyme activity deficiency in adrenal and gonadal glands in Japanese patients with 17alpha-hydroxylase deficiency[J].Endocrinol Jpn,1989,36(4):515-536.
[13]Athanasoulia AP,Auer M,Riepe FG,et al.Rare missense P450c17(CYP17A1)mutation in exon 1as a cause of 46,XY disorder of sexual development:implications of breast tissue unresponsiveness despite adequate estradiol substitution[J].Sex Dev,2013,7(4):212-215.
[14]Qiao J,Han B,Liu BL,et al.A unique exonic splicing mutation in the CYP17A1 gene as the cause for steroid 17{alpha}-hydroxylase deficiency[J].Eur J Endocrinol,2011,164(4):627-633.
[15]Turkkahraman D,Guran T,Ivison H,et al.Indentification of a novel large CYP17A1deletion by MLPA analysis in a family with classic 17α-hydroxylase deficiency[J].Sex Dev,2015,9(2):91-97.
[16]Zhang M,Sun S,Liu Y,et al.New,recurrent,and prevalent mutations:clinical and molecular characterization of 26Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency[J].J Steroid Biochem Mol Biol,2015,150(6):11-16.
[17]郑瑞芝,赵志刚,汪艳芳,等.先天性肾上腺皮质增生症6例临床分析[J].中华实用诊断与治疗杂志,2010,24(4):399-402.