卵巢早衰的常染色体原因Autosomal causes of premature ovarian failure转载2008-02-22

许多不同的常染色体基因可以导致卵巢早衰，而且可以从大鼠基因中推论而来，原发闭经的46，XX卵巢早衰(性腺发育不全)的可能的鉴别诊断。

Many different autosomal genes can lead to premature ovarian failure, and can be inferred from rat genes, the possible differential diagnosis of 46, XX ovarian premature failure(gonadal hypoplasia).

X-性腺发育不全的种类　Type of X-gonad hypoplasia

一、XX性腺发育不全，没有体征异常、伴有神经感受性耳聋(perrault综合征)、伴共济失调(异原性)、其他畸形综合征。

First, XX gonadal hypoplasia, no abnormal signs, accompanied by neurosensory deafness(Perrault syndrome), accompanied by ataxia(heterogenicity), and other deformity syndrome.

二、XX性腺发育不全II, XX gonadal hypoplasia

孟德尔多向性异常的一部分Mengdeerduo, part of a sexual anomaly.

FSH受体突变(FSHR)FSH receptor mutation(FSHR)

LH受体突变(LHR)LH receptor mutation(LHR)

睑裂窄小综合症Small blepharotomy syndrome

三、在两性均有性腺细胞缺乏(46XX)III. Glandular cell deficiency in both sexes(46XX)

没有体征异常No signs.

秃头小头和个子矮Hypertension and deafness

高血压和耳聋Bald.

Small head and short.

无性腺(46XX)Asexual glands(46XX)

四、肾上腺和卵巢合成障碍Adrenal and ovarian synthesis disorders

17a羟化酶(cyp7)17a hydroxylase(cyp7)

芳香化梅Aromatic plum

五、胚胎时代谢异常Embryonic temporal metabolic abnormalities

半乳糖血症galactosemia

磷酸甘露醇变位酶缺乏Lack of mannitol phosphate mutase

六、动态突变(重复三连体)Dynamic Mutations(Repeating Three Alliances)

脆 X综合征Crispy X syndrome

肌强直性萎缩myomuscular atrophy

七、卵巢特异性自身免疫性疾病VII. Ovary specific autoimmune diseases

八、多腺体自身免疫综合症(卵巢早衰)VIII. Multiple gland autoimmune syndrome(ovarian premature failure)

九、常染色体三体IX. autosomal trisomes

13三体13 bodies

18三体18 bodies

性腺发育异常在组织学上和具有异常染色体核型的46，XX个体相似，多病例排除了嵌合体的可能。这些患者，尤其是不伴有躯体异常者可统称为XX性腺发育不全。

Abnormal gonadal development is similar in histology to 46 and XX individuals with abnormal chromosomal nuclei, and many cases rule out the possibility of chimera. These patients, especially those without physical abnormalities, can be collectively referred to as XX gonadal hypoplasia.

有许多类型的46，XX性腺发育不全，但不伴有合并躯体异常的XX性腺发育不全大多是常染色体隐性遗传。患者身高正常(平均身高165cm);通常不具有Turner。体征。经常见到有家系报道提示与常染色体隐性遗传基因有关。分层分析提示姐妹的分层比率为0.16。2/3的46，XX性腺发育不全是遗传性的。非遗传性表型可能是由于感染、梗塞或浸润、自身免疫现象。

There are many types of 46, XX gonadal hypoplasia, but most of the XX gonadal hypoplasia that is not accompanied by an abnormal body is autosomal recessive inheritance. The patient's height was normal(average height 165cm); Usually doesn't have Turner. Signs. It is often seen that genealogical reports suggest that autosomal recessive genes are related. The stratification analysis indicated that the stratification ratio of the sisters was 0.16. 2/3 of 46, XX gonadal hypoplasia is hereditary. Non-hereditary phenotypes may be due to infection, infarction or infiltration, and autoimmune phenomena.

XX性腺发育不全中生殖细胞不能持续存在的机制不清。但存在很多假说。有丝分裂异常可以在相对正常的妇女中表现为卵巢早衰和不育。其他解释还包括生殖细胞迁徙障碍、异常的结缔组织环境、促性腺激素受体异常。

The mechanism that germ cells can not continue to exist in XX gonadoplasia is unclear. But there are many hypotheses. Mitotic abnormalities can appear as premature ovarian failure and infertility in relatively normal women. Other explanations include germ cell migration disorders, abnormal connective tissue environments, and gonadotropin-receptor abnormalities.

其临床表现不一。一些家族内姐妹之一为条索状性腺，而另一位可以原发闭经、极度卵巢发育不良(可能有极少量卵泡)。如果突变基因与XX性腺发育不全有关，就可以有不同表观，该基因与散发性卵巢早衰有关。

Its clinical manifestations are different. One of the sisters in some families is a rosette gland, while the other can have primary amenorrhea and extreme ovarian dysplasia(possibly with a very small amount of follicles). If the mutated gene is related to the incomplete development of the XX gland, there can be different appearances. This gene is related to the premature failure of the emitting ovary.

识别引起不同形式的XX性腺发育不全的常染色体基因很困难。XX性腺发育不全的常染色体易位偶尔会出现于家系中。性腺发育不全散发病例与常染色体相互易位有关，但受累的染色体并不相同。可采用多态性DNA标志物进行全基因组的姐妹配对基因分析(双核;单核重复)。使用姐妹配对分析.仅有50～100个家庭应进行染色体分析以识别特殊的染色体区域。已经成功地运用这一方法阐述了FSH受体突变导致的XX性腺发育不全病例。大鼠基因宿主也可能与之有关，可以预测人类的同源等位基因也存在异常，但其方式经常与预测的完全不同。系统识别和分析cDNA文库的卵巢特异基因、使用大鼠基因敲除技术和人类基因序列分析可以提供更系统的资料。

It is difficult to identify autosomal genes that cause different forms of XX gonadal hypoplasia. The autosomal translocation of the incomplete development of the XX gonad occasionally appears in the family. Cases of gonadal hypoplasia are related to autosomal translocation, but the involved chromosomes are not the same. Polymorphic DNA markers can be used for genome-wide sister pairing gene analysis(binuclear; Single core repetition). Using sister pairing analysis. Only 50 to 100 families should perform chromosome analysis to identify special chromosomal regions. This method has been successfully used to elucidate the case of XX gonadoplasia caused by FSH receptor mutation. The rat gene host may also be related to this, and it can predict that human homologous alleles also have abnormalities, but their methods are often completely different from those predicted. Systematic identification and analysis of ovary specific genes in cDNA libraries, the use of rat gene knockout techniques, and human gene sequence analysis can provide more systematic information.