新复合杂合突变致非经典型21-羟化酶缺陷症

A novel heterozygous complex mutation of CYP21 gene may cause non-classical 21-hydroxylase deficiency

目的分析1例不典型表型的21-羟化酶缺陷症(210HD)患者的诊断过程和分子遗传学资料。方法根据患者临床资料、激素测定及影像学资料确诊,PCR产物直接测序方法检测CYP21基因突变。结果患者为老年女性,以高血压就诊;基础激素测定示孕酮、睾酮、雄烯二酮、空腹17-羟孕酮等高于正常水平;双侧肾上腺结节样增生;快速ACTH兴奋试验显示,激发后17-羟孕酮水平为68.3μg/L。基因测序发现,CYP21基因编码区C1187T(R356W)杂合突变,合并启动子区域C-125T,G-112A,T-109C三个位点相联杂合突变,该复合杂合突变类型尚未见文献报道。结论CYP21基因编码区C1187T杂合突变合并启动子区域C-125T,G-112A,T-109C三位点相联杂合突变可能与不典型表现的21OHD的发生有关。

Objective To investigate the clinical and genetic characteristics of a case with non-classical 21-hydroxylase deficiency （21OHD）. Methods Clinical features and laboratory data were obtained from a patient with non-classical 21OHD, and the promoter and coding areas of CYP21 gene were sequenced. Results The old female patient presented with hypertension. The laboratory examinations showed that plasma androstenedione, testosterone, progesterone and 17-hydroxy progesterone （17OHP） were increased. CT scan revealed bilateral adrenal nodular enlargement. Furthermore, rapid ACTH stimulation test showed that the plasma 17OHP concentration was further increased up to 68. 3 μg/L. Sequencing analysis showed a Cl187T （R356W） substitution at exon 8 and the C - 125T, G - 112A, T - 109C variations in the promoter of CYP21 gene, which was not previous reported. Conclusion The combined heterozygous mutations, C1187T at exon 8 and C - 125T, G -112A, T-109C in promoter, seem to be associated with non-classical 21OHD phenotype.