一种新复合杂合突变导致21-羟化酶缺陷症

目的探讨1例单纯男性化型21-羟化酶缺陷症(21-OHD)基因突变的类型和特点及临床表型与基因突变类型之间的关系。方法收集患者的临床资料,提取外周血白细胞DNA,用PCR方法扩增CYP21A2基因的10个外显子及内含子边界,测序鉴定CYP21A2基因突变位点,进一步分析突变位点与临床表型的关系。结果患者的临床表现主要为外阴发育异常。基因测序结果显示为复合杂合突变,其一个等位基因为c.515 T>A,p.I172N,另一个等位基因为c.593 T>G,p.L198X,此种复合杂合突变主要引起单纯男性化表现。p.L198X是至今尚未见报道的一种新突变。结论发现了CYP21A2基因一种新的突变p.L198X,丰富了CYP21A2基因突变数据库。同时从分子遗传学方面证实了对患者的诊断,患者基因型能很好地解释其临床表现。

A novel compound heterozygous mutations causing 21-hydroxylase deficiency

Objective To investigate the clinical and molecular genetic characteristics of a Chinese patient with 21-hydrosylase deficiency(21-OHD).Methods Clinical features and laboratory data were collected from that patient.Ten exons and the boundaries of exon-intron of CYP21A2 gene were amplified by PCR and sequenced.The correlation between clinical characteristics and genotype was analyzed.Results The female patient was diagnosed as 21-OHD with simple-virilizing form according to the clinical manifestation.DNA sequencing results showed a heterozygous mutation.One allele of the patient contained a base transversion(T>A) at c.515 and led to a missense mutation of Ile to Asn at the 172th amino acid.The an other allele had one base transversion(T>G) at c.593 and led to a nonsense mutation at the 198th codon,which is a new mutation.The novel compound heterozygous mutations cause the simple-virilizing form of congenital adrenal hyperplasia.Conclusions Through CYP21A2 gene analysis,a new mutation causing 21-OHD was found,which broadened the mutation database and the clinical diagnosis of 21-OHD was confirmed.