Validation of the short forms of the Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire in Estonian.

INTRODUCTION AND HYPOTHESIS: Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7) are reliable instruments for evaluating the quality of life in women with pelvic organ prolapse (POP). They have been translated and validated in many languages. The study was aimed at validating the Estonian translations of the PFDI-20 and PFIQ-7 tools. METHODS: The questionnaires were translated into Estonian using a multistep translation method. A total of 132 women were enrolled: patients with diagnosed POP (n=57) were allocated to test-retest reliability analyses, and those with no POP signs (n=88) completed the questionnaire only once. The total scores of questionnaires and their subscales of both patient and reference groups were compared. Item response rate, floor and ceiling effects, corrected item-total correlations, internal consistency, and convergent and discriminant validity were analyzed. The study was approved by the Ethics Committee of Human Research of the University Clinic of Tartu, Estonia, and informed consent was obtained from each participant. RESULTS: The translated questionnaires demonstrated good internal consistency (Cronbach's α values 0.77-0.93). The item response rate was 99%. Intra-class correlations (ICC) were strong for PFDI-20 and PFIQ-7 and their subscales ranged from 0.86 to 0.96. Construct validity of the tools demonstrated by manyfold higher scores among patients with POP compared with women without POP (p<0.0001). CONCLUSIONS: The Estonian versions of the PFDI-20 and PFIQ-7 tools are reliable and valid instruments for assessing the quality of life in women with POP.

Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene.

BACKGROUND: Benign metastasizing leiomyoma (BML) is an orphan neoplasm commonly characterized by pulmonary metastases consisting of smooth muscle cells. Patients with BML have usually a current or previous uterine leiomyoma, which is therefore suggested to be the most probable source of this tumour. The purpose of this case report was to determine the possible genetic grounds for pulmonary BML. CASE PRESENTATION: We present a case report in an asymptomatic 44-year-old female patient, who has developed uterine leiomyoma with subsequent pulmonary BML. Whole exome sequencing (WES) was used to detect somatic mutations in BML lesion. Somatic single nucleotide mutations were identified by comparing the WES data between the pulmonary metastasis and blood sample of the same BML patient. One heterozygous somatic mutation was selected for validation by Sanger sequencing. Clonality of the pulmonary metastasis and uterine leiomyoma was assessed by X-chromosome inactivation assay. CONCLUSIONS: We describe a potentially deleterious somatic heterozygous mutation in bone morphogenetic protein 8B (BMP8B) gene (c.1139A > G, Tyr380Cys) that was identified in the pulmonary metastasis and was absent from blood and uterine leiomyoma, and may play a facilitating role in the metastasizing of BML. The clonality assay confirmed a skewed pattern of X-chromosome inactivation, suggesting monoclonal origin of the pulmonary metastases.

The influence of menstrual cycle and endometriosis on endometrial methylome.

BACKGROUND: Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes, and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. RESULTS: Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases from 31 patients with endometriosis and 24 healthy women. The DNA methylation profile of patients and controls was highly similar and only 28 differentially methylated regions (DMRs) between patients and controls were found. However, the overall magnitude of the methylation differences between patients and controls was rather small (Δß ranging from -0.01 to -0.16 and from 0.01 to 0.08, respectively, for hypo- and hypermethylated CpGs). Unsupervised hierarchical clustering of the methylation data divided endometrial samples based on the menstrual cycle phase rather than diseased/non-diseased status. Further analysis revealed a number of menstrual cycle phase-specific epigenetic changes with largest changes occurring during the late-secretory and menstrual phases when substantial rearrangements of endometrial tissue take place. Comparison of cycle phase- and endometriosis-specific methylation profile changes revealed that 13 out of 28 endometriosis-specific DMRs were present in both datasets. CONCLUSIONS: The results of our study accentuate the importance of considering normal cyclic epigenetic changes in studies investigating endometrium-related disease-specific methylation patterns.