A rare form of CHM, the familial biparental CHM, is not androgenetic but rather is related to mutations in maternal effect genes NLRP7 (NALP7; chromosome 19) and KHDC3L (C6orf221; chromosome 6), which result in global imprinting alteration leading to preferential expression of paternally imprinted genes in villous trophoblast.
Mutations in NLRP7 and KHDC3L confer a complete hydatidiform mole phenotype on digynic triploid conceptions.
Each NLR molecule (NLRP1, NLRP3, NLRP6, NLRP7
, NLRP12, or NAIP/NLRC4) recognizes specific ligands that activate the assembly of the inflammasome.
Sensor protein can be formed by either members of the Nod-like receptor family (NLRP1, NLRP2, NLRP3, NLRC4, NLRP6, NLRP7
, etc.) or the PYHIN family members AIM2 and IFI16 .
The spectrum of NLRP7
mutations in French patients with recurrent hydatidiform mole.
NLRP7 and the genetics of post-molar choriocarcinomas in Senegal.
NLRP7 and the genetics of hydatidiform moles: recent advances and new challenges.
NLRPs are a subgroup of NLRs constituted by proteins such as NLRP1, NLRP3, NLRP4, NLRP6, NLRP7, and NLRP12 that are involved in the formation of multiprotein complexes termed inflammasomes .
NLRP7 is only present in human peripheral blood mononuclear cells after LPS and IL-1/3 stimulation .
"To the best of our knowledge, this report establishes for the first time that oocyte donation can enable women with familial recurrent hydatidiform moles due to NLRP7 mutations to achieve a normal pregnancy," Ms.
The study also shows "that the major role of NLRP7 in pregnancy is in the developing oocyte," they said.
(16) Genetic studies on rare families with recurrent HM have led to the mapping of a major maternal recessive locus to 19q13.4 in several ethnic groups, (17-19) with the subsequent identification of the causative gene, NLRP7
(nucleotide-binding, leucine-rich repeat, pyrin domain).