A maternally inherited autosomal point mutation in human phospholipase C zeta (PLC?) leads to male infertility.
Ontology highlight
ABSTRACT: BACKGROUND:Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLC?). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLC?(H398P)), leading to abnormal PLC? function and infertility. METHODS AND RESULTS:Here, using a combination of direct-sequencing and mini-sequencing of the PLC? gene from the patient and his family, we report the identification of a second PLC? mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLC?(H233L)), which is predicted to disrupt local protein interactions in a manner similar to PLC?(H398P) and was shown to exhibit abnormal calcium oscillatory ability following predictive 3D modelling and cRNA injection in mouse oocytes respectively. We show that PLC?(H233L) and PLC?(H398P) exist on distinct parental chromosomes, the former inherited from the patient's mother and the latter from his father. Neither mutation was detected utilizing custom-made single-nucleotide polymorphism assays in 100 fertile males and females, or 8 infertile males with characterized oocyte activation deficiency. CONCLUSIONS:Collectively, our findings provide further evidence regarding the importance of PLC? at oocyte activation and forms of male infertility where this is deficient. Additionally, we show that the inheritance patterns underlying male infertility are more complex than previously thought and may involve maternal mechanisms.
SUBMITTER: Kashir J
PROVIDER: S-EPMC3241606 | biostudies-literature | 2012 Jan
REPOSITORIES: biostudies-literature
ACCESS DATA
