Muelleriana aplasia and hyperandrogenism (Müllerian aplasia and hyperandrogenism) - Gen WNT4.
The muelleriana and hyperandrogenism aplasia is a disease affecting the female reproductive system. This alteration is due to abnormal development of the Mullerian ducts. Women with Mullerian aplasia and hyperandrogenism usually have an underdeveloped or absent uterus and may also have abnormalities in other reproductive organs. Women with this disease have normal female external genitalia, and develop breasts and pubic hair at puberty normally. However, primary amenorrhea manifest and you will probably never have a menstrual period. Affected women are sterile and also have hyperandrogenism, which can lead to acne and facial hirsutism. Some affected individuals may have kidney abnormalities.
This process is due to mutations in the gene WNT4, located on the short arm of chromosome 1 (1p36.23-p35.1). This gene belongs to a family of WNT genes that play a critical role in development before birth. Wnt genes encode proteins involved in chemical signaling pathways in the body. These pathways control the activity of certain genes and regulate interactions between cells during embryonic development. Specifically, the WNT4 gene encodes a protein that is important for the formation of the female reproductive system, kidney, and various hormone - producing glands. During the development of the female reproductive system, the WNT4 protein regulates the formation of Mullerian ducts. This protein is also involved in the development of the ovaries, from before birth to adulthood, and it is important for the development and maintenance of oocytes. Furthermore, WNT4 protein regulates androgen production.
They have identified at least 3 WNT4 gene mutations in people with muelleriana aplasia and hyperandrogenism. These mutations change the amino acids in protein WNT4. It is likely that the altered protein can not be released from the cells, being unable to perform their usual functions. As a result, the loss of regulation by WNT4 probably disrupts the development of the female reproductive system and induces abnormal androgen production, leading to the characteristics of the disease.
Muelleriana aplasia and hyperandrogenism is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. Girls with aplasia and hyperandrogenism Müller not inherit the mutation from his mother, because women with this disorder can not have children. however, it is unclear if an affected person inherits the mutation from his father or is due to new mutations in the gene. Müller aplasia and hyperandrogenism can occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with aplasia muelleriana and hyperandrogenism, by complete PCR amplification of exons WNT4 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).