Recurrent hydatidiform mole (hydatidiform mole Recurrent) - Genes NLRP7 and KHDC3L.
A hydatidiform mole is a benign gestational trophoblastic disease developed during pregnancy, a result of abnormal trophoblastic fertilization characterized by proliferation which makes it impossible to normal embryonic development. Hydatidiform mole recurring occurs when women have at least two abnormal pregnancies described as hydatidiform mole.
Often a hydatidiform mole causes vaginal bleeding in the first trimester of pregnancy. In an ultrasound examination, the placenta appears as numerous small bags, like a bunch of grapes. In some cases, ultrasound does not show fetus, umbilical cord or amniotic sac. Hydatidiform mole must be surgically removed, usually late in the first quarter. After that, there are up to 20% risk that any lingering mola continue to grow and become cancerous tumor called invasive mole. The invasive mole can become gestational choriocarcinoma that can spread to other tissues such as the liver, lungs or brain.
This process is due to mutations in genes NLRP7, located on the long arm of chromosome 19 (19q13.42) and KHDC3L, located on the long arm of chromosome 6 (6q13). Mutations in the gene NLRP7 are the most common cause. Inside oocytes, it is believed that NLRP7 and KHDC3L proteins play a role in the inactivation of certain genes based on genomic imprinting. For most genes, two copies of the gene, one inherited from each parent copy, are active in all cells. However, for a small subset of genes, only one of the two copies is active. For some of these genes, the copy of the father is active, while for others, the copy of the mother is active. It is likely that NLRP7 and KHDC3L proteins are involved in the printing of multiple maternal genes in oocytes, ensuring that they will be inactive in the developing embryo, while corresponding parental genes are active. Furthermore, it is likely that NLRP7 protein involved in the growth, proliferation and cell differentiation. It is believed that this protein plays a role in inflammation and other immune responses by regulating the release of an immune protein called interleukin-1 beta.
There are more than 50 mutations in the gene NLRP7 and at least four mutations in the gene responsible for mola KHDC3L recurrent mole. These genetic changes lead to protein coding with impaired function, which leads to activation of many maternal genes that should not be expressed. As a result, several of the genes that contribute to the development of the embryo do not print correctly, leading to an abnormal gene expression in all pregnancies. Overexpression of multiple genes underlying poor development of fetal placental tissues characteristic of a hydatidiform mole. Furthermore, mutations in the gene cause NLRP7 slow release of interleukin-1 beta, which alters the normal immune response of the organism which recognizes a hydatidiform mole. In some cases of recurrent hydatidiform mole, they have not identified mutations in genes NLRP7 and KHDC3L. In these cases, the cause of the condition is unknown.
This disease is inherited as an autosomal recessive frequency pattern, which means that both copies of the gene in every cell must have mutations to have a recurrent pregnancy hydatidiform mole.
Tests in IVAMI: in IVAMI perform detection of mutations associated with hydatidiform mole recurrent, by complete PCR amplification of the exons of NLRP7 and KHDC3L genes, respectively, 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).