Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees
Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees
复制标题
DOI：
10.1093/hmg/5.12.2039
复制
发表时间：
1996-12-01
影响因子：
3.5
通讯作者：
White, PC
中科院分区：
文献类型：
--
作者：
Day, DJ;Speiser, PW;White, PC
甾体21-羟化酶缺乏症是人类最常见的先天性代谢缺陷之一，21-羟化酶基因（CYP21）突变的特征可以通过聚合酶链反应（PCR）进行遗传诊断，最常见的突变是nt656的A或C转化为第二个内含子的G，导致mRNA的异常剪接。nt656G的纯合子与肾上腺皮质醇和醛固酮合成严重不足、肾上腺雄激素继发性高分泌以及新生儿以生殖器模糊和/或钠消耗为特征的严重形式的先天性肾上腺增生（CAH）有关。在对CAH家族CYP21突变的遗传分析过程中，我们和其他人注意到许多亲属基因型为nt656G纯合子，但没有表现出疾病的临床症状。许多证据使我们提出，假定的无症状nt656G/G个体由于在CYP21的PCR扩增过程中丢失了一个单倍型而被错误分型。对于产前诊断，我们建议使用微卫星分型作为CYP21基因分型的补充，以解决nt656的歧义。
Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man, Characterization of mutations in the 21-hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR), The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns, During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease, A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21, For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.