An etiological analysis of 106 cases with ambiguous genitalia / 中华实用儿科临床杂志

ABSTRACT

Objective To explore the causes of ambiguous genitalia.Methods Clinical data of 106 cases with ambiguous genitalia from Ruijin Hospital of Shanghai Jiaotong University School of Medicine were retrospectively analyzed.DNA fragments of related genes from parts of patients were amplified by means of polymerase chain reaction (PCR) and were directly sequenced to detect gene mutations.Results (1)The 106 ambiguous genitalia patients presented a variety of clinical phenotypes.Karyotype of 42 cases(39.6％)were 46,XX,while 62 cases(58.5％)were 46,XY and 2 cases(1.9％)were abnormal.(2)Forty(95.2％)patients with 46,XX were diagnosed with congenital adrenal hyperplasia(CAH) ;one case(2.4％) was adrenal cortical tumor and one case (2.4％) was 46,XX [sex determining region of Y choromosome (SRY) positive] male syndrome.(3) Fifty-three cases (85.5 ％) out of 46,XY karyotype were directly sequenced with steroid-5-alpha-reductase,alpha polypeptide 2 gene (SRD5A2),androgen receptor gene (AR) and steroidogenic factor-1 gene(SF-1).Sequencing analysis of SRD5A2 revealed 8 patients with compound heterozygous or homozygous mutations.A patient carried a novel missense mutation of SF-1 and another patient had a mutation of AR.(4) One abnormal karyotype was 46,XX/46,XY and the other was 46,XX/46,XY/46,X.+ may.ish (DYZ3 +) (DXZ1-).Conclusions (1) CAH is the most common cause of genital ambiguity in 46,XX patients but some rare causes such as adrenal cortical tumors or SRY positive should not be ignored.(2) To find the causes of 46,XY genital ambiguity,direct DNA sequencing analysis of candidate genes would be the better choice because of the complicate pathogenesis.(3)Abnormal karyotype also can lead to ambiguous genitalia.