Molecular Genetic Studies Of Pelvic Organ Prolapse

Background and ObjectivesPelvic organ prolapse(POP)is a common female pelvic floor dysfunction.The prevalence of symptomatic prolapse is 9.56%.Current evidence suggests that both genetic and environmental factors contribute to POP.However,genetic predisposing factors remain to be further explored since no definitive conclusions have been reached so far.Materials and MethodsWe found eleven POP families from patients who had been evaluated for POP at Peking Union Medical College Hospital from August 2016 to January 2017.Clinical information and peripheral blood samples were collected from family members.We performed whole-genome sequencing(WGS)in eleven probands for pathogenic gene screening.Sanger sequencing was then conducted in probands and relevant relatives for single nucleotide polymorphism(SNP)validation.Candidate genes related to large deletions were further quantified via quantitative real-time PCR(qPCR).ResultsTwenty-six SNPs in ten candidate genes(COL6A1,COL6A6,COL7A1,LAMA5,LAMB1,LAMC3,FN1,ITGB4,THBS1 and ADAMTS2)were identified through WGS.COL6A1,COL6A6,LAMA5,FN1,THBS1 and ADAMTS2 were considered candidate pathogenic genes after Sanger sequencing.Six candidate genes(LAMC1,COLIA1,COL3A1,COL5A2,ELN and TNXB)located in large deletions were identified through WGS.However,they were most likely to be false positive results as they couldn't be verified by qPCR.ConclusionPOP may exist as a monogenic disease in some families with high genetic heterogeneity.