Genetics/Basic Defects 遗传学/基本缺陷
- 常见表型
——small phallus with severe chordee 阴茎短小（足月新生儿<3.5 cm）合并严重下弯
——posterior hypospadias 尿道下裂
——poorly formed bifid scrotum 阴囊对裂（阴囊左右两部分分离）
——with or w/o testicular maldescent 可伴有睾丸下降不良
- The commonest cause is a group of disorders known as androgen insensitivity syndrome (AIS) 最常见的疾病是雄激素不敏感综合征AIS
——an X-linked disorder resulting from peripheral resistance to androgen action 一种X染色体连锁的遗传病导致外周器官抵抗/耐受雄激素的作用
——either from mutations in the androgen receptor gene or elsewhere in the molecular pathway 既可以是雄激素受体基因（AR）本身的突变 也可以是相关分子通路上其他基因发生突变
a defect in the conversion of dihydrotestosterone to 5α-androstanediol remains to be seen （AIS）也可以是由于二氢睾酮到Adiol转化出现异常导致
5α-reductase deficiency is another cause of undervirilization 5α还原酶缺陷症是另一种可能的原因
——an autosomal recessive defect resulting in deficient dihydrotestosterone necessary in the virilization of the external genitalia in early embryogenesis 它是一种常染色体隐性疾病 引起二氢睾酮缺乏 而二氢睾酮尤其在胚胎发育早期的外生殖器形成（男性化）中发挥作用
- Causes of undervirilization of male infant 男婴男性化不足原因——来自Chi, C et al. (2008) NeoReviews, 9, e78–e84.
a. Defects in testosterone production: 睾酮生成异常
——Leydig cell hypoplasia/agenesis 睾丸间质细胞功能不全/异常发生
——Defects in testicular and adrenal steroidogenesis 睾丸和肾上腺类固醇代谢异常
——steroid acute regulatory (StAR) protein deficiency, 3β-hydroxysteroid dehydrogenase deficiency, 17α-hydroxylase/17,20lyase deficiency, 17α-hydroxysteroid dehydrogenase (ketosteroid reductase) deficiency 包括类固醇生成急性调节蛋白缺陷、3β-羟基类固醇脱氢酶缺陷、17α-羟化酶/17,20-裂解酶缺陷（简称17OHD）、17β-羟基类固醇脱氢酶缺陷
b. Defects in testosterone metabolism: 睾酮代谢异常
——5α-reductase deficiency 5α还原酶缺陷症
c. Defects in testosterone action: （细胞对）睾酮反应异常
——androgen insensitivity syndrome 雄激素不敏感综合征AIS
d. Exogenous estrogen/progestin exposure 外源性雌激素/合成黄体酮暴露
- 46,XY DSD, testicular development disorders: causative genes and phenotypes 46,XY性发育异常疾病及睾丸发育相关疾病——致病基因和临床表型——来自Ono, M & Harley, VR. (2013) Nat Rev Endocrinol. 2013 9(2):79-91.
a. ARX (Xp22.13, testicular factor (TF)): dysgenetic testis, no Müllerian structures, ambiguous external genitalia, lissencephaly, epilepsy, and temperature instability ARX基因：睾丸发育异常、无缪勒氏管结构、外生殖器模糊、无脑回、癫痫 和体温不稳
b. ATRX (Xq13.3, chromatin-remodeling protein): dysgenetic testis, no Müllerian structures, female-like or ambiguous or male-like external genitalia, α-thalassemia, mental retardation, and dysmorphic face ATRX基因：睾丸发育异常、无缪勒氏管结构、外生殖器女性化/模糊/男性化均可、α地贫、智力障碍 和面部畸形
c. CBX2 (17q25, polycomb protein): normal ovaries, Müllerian structures present, and female-like external genitalia CBX2基因：正常卵巢、有缪勒氏管结构 和外生殖器女性化
d. DHH (12q13.1, signaling molecule): dysgenetic testis, Müllerian structures present, female-like external genitalia, and minifascicular neuropathy DHH基因：睾丸发育异常、有缪勒氏管结构、外生殖器女性化 和小型神经束型神经病变
e. DMRT1 (9p24.3, TF): dysgenetic testis or ovotestis +/- Müllerian structures, female-like or ambiguous or male-like external genitalia, facial abnormality, mental retardation, and microcephaly DMRT1基因：睾丸发育异常或卵睾？、有/无缪勒氏管结构、外生殖器女性化/模糊/男性化均可见、面部异常、智力障碍 和小头畸形
f. GATA4 (8p23.1-p22, TF): dysgenetic testis, Müllerian structures absent, ambiguous or male-like external genitalia, and congenital heart disease GATA4基因：睾丸发育异常、缪勒氏管结构缺如、外生殖器模糊/男性化均可见和先天性心脏病
g. MAMLD1 (Xq28, transcriptional co-activator): normal function of sex organs, no Müllerian structures, and hypospadias MAMLD1基因：性腺器官功能正常、无缪勒氏管结构 和尿道下裂
h. MAP3K1 (5q11.2, kinase): dysgenetic testis, Müllerian structures may be present, and female-like or ambiguous or male-like external genitalia MAP3K1基因：睾丸发育异常、可有缪勒氏管结构 和外生殖器女性化/模糊/男性化均可见
i. NROB1 (Xp21.3, nuclear receptor (NR)/TF): dysgenetic testis or ovary +/- Müllerian structures, female-like or ambiguous or male-like external genitalia, cleft palate, and mental retardation NROB1基因：睾丸或卵巢发育异常、有/无缪勒氏管结构、外生殖器女性化/模糊/男性化均可见、腭裂 和智力障碍
j. NR5A1 (9q33, NR/TF): dysgenetic testis +/- Müllerian structures, female-like or ambiguous or male-like external genitalia, and +/- adrenal insufficiency NR5A1基因：睾丸发育异常、有/无缪勒氏管结构、外生殖器女性化/模糊/男性化均可见 和有/无肾上腺功能不全
k. SOX9 (17q24-q25, TF): dysgenetic testis or ovotestis, +/- Müllerian structures, female-like or ambiguous external genitalia, and campomelic dysplasia SOX9基因：睾丸发育异常或卵睾？、有/无缪勒氏管结构、外生殖器女性化/模糊均可见 和广泛性先天发育不良CD
l. SRY (Yp11.3, TF): dysgenetic testis or ovotestis, +/ Müllerian structures, and female-like or ambiguous external genitalia SRY基因：睾丸发育异常或卵睾？、有/无缪勒氏管结构 和外生殖器女性化/模糊均可见
m. WNT4 (1p35, signaling molecule): dysgenetic testis, Müllerian structures present, ambiguous external genitalia, cleft lips and palate, tetralogy of Fallot, intrauterine growth retardation, microcephaly, and mental retardation WNT4基因：睾丸发育异常、有缪勒氏管结构、外生殖器模糊、唇腭裂、法洛四联症、宫内生长受限、小头畸形 和智力障碍
n. WT1 (11p13, TF): dysgenetic testis +/- Müllerian structures, female-like or ambiguous external enitalia, Wilms tumor, renal abnormalities, and gonadal tumors (WAGR, Denys-Drash, and Frasier syndromes) WT1基因：睾丸发育异常、有/无缪勒氏管结构、外生殖器女性化/模糊均可见、肾母细胞瘤、肾脏异常 和生殖腺肿瘤
o. WWOX (16q23.3-q24.1, oxidoreductase): dysgenetic testis, no Müllerian structures, and female-like external genitalia WWOX基因：睾丸发育异常、无缪勒氏管结构 和外生殖器女性化
