Zenteno Juan Carlos, Carranza-Lira Sebastian, Kofman-Alfaro Susana
Department of Genetics, Hospital General de Mexico-Facultad de Medicina UNAM, Dr. Balmis 148, Col. Doctores, 06726 Mexico City, Mexico.
Arch Gynecol Obstet. 2004 May;269(4):270-3. doi: 10.1007/s00404-002-0456-7. Epub 2002 Dec 19.
Müllerian agenesis, also named the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) or vaginal aplasia, is the second most common cause of primary amenorrhea. It is characterized by the congenital absence of the Müllerian structures including the Fallopian tubes, the uterus, and the internal portion of the vagina in an otherwise normally feminized 46,XX subject. Most cases are sporadic in inheritance, but the occurrence of some patients with chromosomal translocations or even familial aggregates suggest a genetic basis for the disease, although the etiology of the disease is still unknown. It has been suggested that activating mutations in the anti-Müllerian hormone (AMH) or in its receptor (AMHRII) are potential sources for the defect.
In this study we describe the molecular analysis of both the AMH and AMHR genes in a group of 15 patients with Müllerian agenesis. After sequencing all exons and exon/intron junctions of both genes, we were not able to detect any deleterious mutation.
Five new polymorphisms, 2 of them in the AMHRII gene and 3 of them in the AMH gene, were identified. No significant differences between patients and controls were observed in the frequency of a given polymorphism.
This work reinforces the view that molecular defects in the AMH or AMHR are unlikely sources for the MRKHS syndrome.
苗勒管发育不全,也称为迈耶-罗基坦斯基-库斯特-豪泽综合征(MRKHS)或阴道发育不全,是原发性闭经的第二大常见原因。其特征是在其他方面表现正常的46,XX女性个体中,先天性缺乏包括输卵管、子宫和阴道内部的苗勒管结构。大多数病例为散发性遗传,但一些伴有染色体易位甚至家族聚集性发病的患者提示该病存在遗传基础,尽管其病因仍不清楚。有人提出抗苗勒管激素(AMH)或其受体(AMHRII)的激活突变可能是该缺陷的潜在原因。
在本研究中,我们描述了对15例苗勒管发育不全患者的AMH和AMHR基因的分子分析。在对两个基因的所有外显子以及外显子/内含子连接区进行测序后,我们未检测到任何有害突变。
鉴定出5个新的多态性位点,其中2个位于AMHRII基因,3个位于AMH基因。在特定多态性位点的频率上,患者与对照组之间未观察到显著差异。
这项研究进一步支持了以下观点,即AMH或AMHR的分子缺陷不太可能是MRKHS综合征的病因。