ABSTRACT
OBJECTIVE@#To explore the genetic basis of two fetuses with an osteogenesis imperfecta (OI) phenotype.@*METHODS@#Two fetuses diagnosed at the Affiliated Hospital of Weifang Medical College respectively on June 11, 2021 and October 16, 2021 were selected as the study subjects. Clinical data of the fetuses were collected. Amniotic fluid samples of the fetuses and peripheral blood samples of their pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing (WES) and Sanger sequencing were carried out to identify the candidate variants. Minigene splicing reporter analysis was used to validate the variant which may affect the pre-mRNA splicing.@*RESULTS@#For fetus 1, ultrasonography at 17+6 weeks of gestation had revealed shortening of bilateral humerus and femurs by more than two weeks, in addition with multiple fractures and angular deformities of long bones. WES revealed that fetus 1 had harbored a heterozygous c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in exon 49 of the COL1A1 gene (NM_000088.4). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting) for disrupting the downstream open reading frame resulting in premature translational termination, being de novo in origin, and lacking records in the population and disease databases.For fetus 2, ultrasonography at 23 weeks of gestation also revealed shortening of bilateral humerus and femurs by one and four weeks, respectively, in addition with bending of bilateral femurs, tibias and fibulas. Fetus 2 had harbored a heterozygous c.1557+3A>G variant in intron 26 of the COL1A2 gene (NM_000089.4). Minigene experiment showed that it has induced skipping of exon 26 from the COL1A2 mRNA transcript, resulting in an in-frame deletion (c.1504_1557del) of the COL1A2 mRNA transcript. The variant was inherited from its father and had been previously reported in a family with OI type 4. It was therefore classified as a pathogenic variant (PS3+PM1+PM2_Supporting+PP3+PP5).@*CONCLUSION@#The c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in the COL1A1 gene and c.1557+3A>G variant in the COL1A2 gene probably underlay the disease in the two fetuses. Above findings not only have enriched the mutational spectrum of OI, but also shed light on the correlation between its genotype and phenotype and provided a basis for genetic counseling and prenatal diagnosis for the affected pedigrees.
Subject(s)
Pregnancy , Female , Humans , Osteogenesis Imperfecta/genetics , Collagen Type I, alpha 1 Chain , Collagen Type I/genetics , Mutation , FetusABSTRACT
INTRODUCTION: Sexual dysfunction is a common problem affecting women's quality of life. However, reports on sexual dysfunction and its risk factors in Chinese women are scarce in the literature. AIM: To identify the potential risk factors for low sexual function in urban Chinese women. METHODS: A cross-sectional hospital-based survey was conducted in Nanjing, China. Data on sexual function and related variables of 1,457 women from the urban district of Nanjing city were obtained. Potential risk factors for low sexual function were determined using multiple logistic regression analysis. MAIN OUTCOME MEASURE: The Female Sexual Function Index (FSFI) was used to evaluate sexual function, and the median of the FSFI score was used as a cutoff to define women with low sexual function. RESULTS: The mean FSFI total score was 23.25 ± 4.00 (median = 22.8). Multivariate analysis showed that age (odds ratio [OR] 1.840 for 40-49 years; 5.006 for 50-60 years), depression (OR 1.896), low education level (primary or secondary school only, OR 1.450), alcohol use (OR 2.671), menopause or postmenopause (OR 3.157), chronic medical disease (OR 1.605), poor health status of partner (OR 3.358), presence of sexual dysfunction in partner (OR 4.604), dystocia (OR 3.109), and living apart from the partner (OR 1.316) were independent risk factors for low sexual function of women in urban China. By contrast, better communication with the partner regarding sex (OR 0.531) was a protective factor. CONCLUSION: Low sexual function for urban Chinese women was associated with multiple variables. Women who communicated more frequently with their partner were less likely to have low sexual function.
