Whole-exome sequencing of consanguineous families with infertile men and women identifies homologous mutations in SPATA22 and MEIOB

AbstractSTUDY QUESTIONCan whole-exome sequencing (WES) reveal pathogenic mutations in two consanguineous Pakistani families with infertile patients?SUMMARY ANSWERA homozygous spermatogenesis associated 22 (SPATA22) frameshift mutation (c.203del), which disrupts the interaction with meiosis specific with OB-fold (MEIOB), and aMEIOB splicing mutation (c.683-1G>A) that led to loss of MEIOB protein cause familial infertility.WHAT IS KNOWN ALREADYMEIOB and SPATA22, direct binding partners and functional collaborators, form a meiosis-specific heterodimer that regulates meiotic recombination. The protein stability and the axial localization of MEIOB and SPATA22 depend on each other.Meiob andSpata22 knockout mice have the same phenotypes: mutant spermatocytes can initiate meiotic recombination but are unable to complete DSB repair, leading to crossover formation failure, meiotic prophase arrest, and sterility.STUDY DESIGN, SIZE, DURATIONWe performed WES for the patients and controls in two consanguineous Pakistani families to screen for mutations. The pathogenicity of the identified mutations was assessed byin vitro assay and mutant mouse model.PARTICIPANTS/MATERIALS, SETTING, METHODSTwo consanguineous Pakistani families with four patients (three men and one woman) suffering from primary infertility were recruited.SPATA22 andMEIOB mutations were screened from the WES data, followed by functional verification in cultured cells and mice.MAIN RESULTS AND THE ROLE OF CHANCEA homozygou...
Source: Human Reproduction - Category: Reproduction Medicine Source Type: research