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目的探讨中国人17α-羟化酶/l7,20-碳链裂解酶缺陷症(17OHD)种族特异性的基因突变特点。方法采集3个无血缘关系的17OHD家系的患者及其亲属的外周血,抽提DNA后,通过PCR、亚克隆测序、限制性酶切片段长度多态性(RFLP)等方法对致病基因17α羟化酶基因(CYP17A1)进行突变分型,并对文献报道的26例中国17OHD患者的资料进行回顾性分析。结果 1号家系先证者为8号外显子487-488-499密码子处9碱基纯合缺失(GACTCTTTCdel),致天冬氨酸-丝氨酸-苯丙氨酸缺失(D487_S488_F489del),翻译后蛋白质肽链长度缩短;2号家系先证者为6号外显子329密码子处TAC→AA,纯合插入缺失突变致酪氨酸→赖氨酸,并在418密码子处提前出现终止密码,形成截短型蛋白(Y329K,418X);3号家系先证者为前两种突变类型的复合突变(Y329K,418X联合D487_S488_F489del)。对文献报道的中国26例17OHD病例进行基因突变分析,发现其基因突变遗传规律有明显的种族特异性:6号外显子受累程度最高,等位基因比例为55.77%(29/52);其次为8号外显子,等位基因比例为40.38%(21/52),6和8号外显子等位基因总占有率达96.15%(50/52);26例患者中,Y329K,418X纯合子共9例(基因型比例为34.62%),D487_S488_F489del纯合子共5例(基因型比例为19.23%),两者相加共14例(基因型比例为53.85%);Y329K等位基因比例为42.31%(22/52),D487_S488_F489del等位基因比例为30.77%(16/52),两者的等位基因比例达73.08%。结论17OHD在中国人中遗传具有种族特异性,第6号外显子TAC329AA突变形成截短型蛋白Y329K,418X和第8号外显子GACTCTTTC del导致D487_S488_F489del为中国人17OHD最常见的两种突变类型。
Objective To investigate the race-specific gene mutation characteristics of 17α-hydroxylase / 17,20-carbon chain lyase deficiency (17OHD) in Chinese. Methods The peripheral blood of patients with unrelated 17OHD pedigrees and their relatives were collected. DNA was extracted and sequenced by PCR, subcloning and restriction fragment length polymorphism (RFLP) Hydroxylase gene (CYP17A1) mutation typing, and reported in the literature of 26 cases of 17OHD patients in China were retrospectively analyzed. Results The first probands of family number 1 were the deletion of aspartic acid-serine-phenylalanine deletion (D487_S488_F489del), the post-translational protein (GACTCTTTCdel) at codon 487-488-499 of exon 8, The length of the peptide chain was shortened; the probands of No. 2 family was TAC → AA at the codon 329 of exon 6, and the tyrosine → lysine was inserted homozygously and the termination codon appeared prematurely at codon 418 to form Truncated type protein (Y329K, 418X); No.3 family probands were compound mutations of the first two types of mutations (Y329K, 418X combined with D487_S488_F489del). Genetic mutations in 26 cases of 17OHD cases reported in the literature were analyzed and found that the genetic rules of the gene mutations were significantly racially specific: exon 6 had the highest degree of involvement and the percentage of alleles was 55.77% (29/52), followed by The exon 8, allele ratio was 40.38% (21/52), the total number of exon 6 and exon allele 96.15% (50/52); 26 patients, Y329K, 418X homozygotes 9 (34.62% of genotypes), 5 of D487_S488_F489del homozygotes (19.23% of genotypes), 14 cases (53.85% of genotypes) were additive, and the proportion of Y329K alleles was 42.31% (22/52). The proportion of alleles in D487_S488_F489del was 30.77% (16/52), and the proportion of the two alleles was 73.08%. Conclusion 17OHD is genetically specific in Chinese. The mutation of exon 6 of TAC329AA to truncated protein Y329K, 418X and exon 8 of GACTCTTTC del resulted in D487_S488_F489del being the two most common mutations in Chinese 17OHD.