在日本先天性醛固酮减少症患者中，CYP11B2基因第8外显子存在一个错义突变（GGC[435甘氨酸]→AGC[丝氨酸]），该突变呈遗传状态。
A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism.
作者信息
Kuribayashi Isao, Kuge Hideaki, Santa Romero Jovel, Mutlaq Aldahoodi Ziyad, Yamasaki Naohito, Furuno Takashi, Takahashi Akio, Chida Shoichi, Nakamura Toshiro, Endo Fumio, Doi Yoshinori, Onishi Saburo, Shizuta Yutaka
机构信息
Department of Medical Chemistry, Kochi Medical School, Kochi, Japan.
出版信息
Horm Res. 2003;60(5):255-60. doi: 10.1159/000074041.
OBJECTIVES
To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated.
METHODS
We analyzed the patients' genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed.
RESULTS
The analysis showed that the patients homozygously retained a missense mutation, Gumacr;GC[435Gly]-->Aumacr;GC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced.
CONCLUSION
These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450(C18) activities causes CMO II deficiency.
目的
为阐明Ⅱ型皮质酮甲基氧化酶（CMOⅡ）缺乏症的潜在分子机制，我们对新诊断为CMOⅡ缺乏症的日本患者进行了研究。
方法
我们分析了患者CYP11B2基因所有9个外显子的基因组DNA序列。此外，还进行了限制性片段长度多态性（RFLP）分析和表达研究。
结果
分析显示，患者在CYP11B2基因中纯合保留了一个错义突变，Gumacr;GC[435Gly]→Aumacr;GC[Ser]。表达研究表明，突变酶的类固醇18-羟化酶/氧化酶活性大幅降低。
结论
这些结果支持该突变导致患者CMOⅡ缺乏症的假说，并且与我们关于P-450（C18）活性部分丧失导致CMOⅡ缺乏症的理论一致。
Zotero 插件