Ordoñez-Sánchez M L, Ramírez-Jiménez S, López-Gutierrez A U, Riba L, Gamboa-Cardiel S, Cerrillo-Hinojosa M, Altamirano-Bustamante N, Calzada-León R, Robles-Valdés C, Mendoza-Morfin F, Tusié-Luna M T
Unidad de Genética de la Nutrición del Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City.
Hum Genet. 1998 Feb;102(2):170-7. doi: 10.1007/s004390050672.
Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated Mexican patients and the corresponding mutant alleles in their parents by amplification of the functional CYP21 gene by PCR, followed by direct sequence analysis. The study included patients diagnosed with the three clinical forms of the disease. Our results revealed: (1) the presence of relatively few mutations or combinations of mutations associated with particular phenotypes; (2) the presence of putative new mutations; (3) the finding of identical genotypes in patients displaying discordant phenotypes; (4) the identification of patients lacking all previous reported mutations; and (5) an apparent high frequency of germ-line mutations. The absence of previously reported mutations in about 22% of the disease alleles, the finding of putative new mutations in some of the patients lacking previously known mutations, and the apparent high prevalence of germ-line mutations make evident the differences in the genetic background leading to this disorder between the Caucasian and the Mexican populations.
类固醇21-羟化酶缺乏症是90%以上先天性肾上腺皮质增生症患者的根本病因，先天性肾上腺皮质增生症是一种肾上腺类固醇生成的遗传性代谢紊乱疾病。我们通过PCR扩增功能性CYP21基因，随后进行直接序列分析，对47名无亲缘关系的墨西哥患者及其父母中的94个突变等位基因进行了特征分析。该研究纳入了被诊断为该疾病三种临床类型的患者。我们的结果显示：（1）与特定表型相关的突变或突变组合相对较少；（2）存在假定的新突变；（3）在表现出不一致表型的患者中发现相同的基因型；（4）鉴定出缺乏所有先前报道突变的患者；（5）明显高频率的生殖系突变。约22%的疾病等位基因中不存在先前报道的突变，在一些缺乏先前已知突变的患者中发现假定的新突变，以及明显高频率的生殖系突变，这些都表明白种人和墨西哥人群中导致这种疾病的遗传背景存在差异。
