CAJ | 학술논문

目的分析外生殖器畸形患儿的临床特征并探讨其发病原因,以期提高该病的诊疗水平.方法收集近几年因外生殖器畸形就诊于上海交通大学医学院附属瑞金医院的106例患儿的资料,总结其临床特征、行染色体核型分析及其他辅助检查.部分患儿抽提外周血基因组DNA进行相关基因突变筛查.结果 (1)106例外生殖器畸形患儿表型多样,从单纯阴蒂肥大/单纯尿道口开口异常,到外生殖器呈间性畸形、性别难辨.染色体核型分析:46,XX 42例(39.6％);46,XY 62例(58.5％);2例(1.9％)染色体核型异常.(2)42例46,XX核型患儿诊断为先天性肾上腺皮质增生症(CAH) 40例(95.2％),肾上腺肿瘤1例(2.4％),另有1例(2.4％)患儿性别决定基因(SRY)阳性.(3)46,XY核型中的53例(85.5％)行5α-还原酶2型基因(SRD5A2)、雄激素受体基因(AR)和类固醇生成因子-1基因(SF-1)突变筛查,发现8例患儿存在SRD5A2突变,存在AR和SF-1突变者各1例.(4)2例染色体异常患儿,1例染色体核型为46,XX/46,XY嵌合型;1例为46,XX/46,XY/46,X.+may.ish(DYZ3+)(DXZ1-)嵌合型.结论 (1)CAH是46,XX核型中呈现外生殖器畸形最常见的病因,少见因素如肾上腺肿瘤、SRY易位等.(2)46,XY核型的外生殖器畸形发病机制复杂,基因突变筛查是明确其病因的最有效方法.(3)染色体异常亦可以引起外生殖器畸形表型.
목적 분석외생식기기형환인적림상특정병탐토기발병원인,이기제고해병적진료수평.방법 수집근궤년인외생식기기형취진우상해교통대학의학원부속서금의원적106례환인적자료,총결기림상특정、행염색체핵형분석급기타보조검사.부분환인추제외주혈기인조DNA진행상관기인돌변사사.결과 (1)106예외생식기기형환인표형다양,종단순음체비대/단순뇨도구개구이상,도외생식기정간성기형、성별난변.염색체핵형분석:46,XX 42례(39.6％);46,XY 62례(58.5％);2례(1.9％)염색체핵형이상.(2)42례46,XX핵형환인진단위선천성신상선피질증생증(CAH) 40례(95.2％),신상선종류1례(2.4％),령유1례(2.4％)환인성별결정기인(SRY)양성.(3)46,XY핵형중적53례(85.5％)행5α-환원매2형기인(SRD5A2)、웅격소수체기인(AR)화류고순생성인자-1기인(SF-1)돌변사사,발현8례환인존재SRD5A2돌변,존재AR화SF-1돌변자각1례.(4)2례염색체이상환인,1례염색체핵형위46,XX/46,XY감합형;1례위46,XX/46,XY/46,X.+may.ish(DYZ3+)(DXZ1-)감합형.결론 (1)CAH시46,XX핵형중정현외생식기기형최상견적병인,소견인소여신상선종류、SRY역위등.(2)46,XY핵형적외생식기기형발병궤제복잡,기인돌변사사시명학기병인적최유효방법.(3)염색체이상역가이인기외생식기기형표형.
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.