Approximately 0.5–1.4% of natal males and 0.2–0.3% of natal females meet DSM-5 criteria for gender dysphoria, with many of these individuals self-describing as transgender men or women. Despite recent improvements both in social acceptance of transgender individuals as well as access to gender affirming therapy, progress in both areas has been hampered by poor understanding of the etiology of gender dysphoria. Prior studies have suggested a genetic contribution to gender dysphoria, but previously proposed candidate genes have not yet been verified in follow-up investigation. In this study, we expand on the topic of gender identity genomics by identifying rare variants in genes associated with sexually dimorphic brain development and exploring how they could contribute to gender dysphoria. To accomplish this, we performed whole exome sequencing on the genomic DNA of 13 transgender males and 17 transgender females. Whole exome sequencing revealed 120,582 genetic variants. After filtering, 441 variants in 421 genes remained for further consideration, including 21 nonsense, 28 frameshift, 13 splice-region, and 225 missense variants. Of these, 21 variants in 19 genes were found to have associations with previously described estrogen receptor activated pathways of sexually dimorphic brain development. These variants were confirmed by Sanger Sequencing. Our findings suggest a new avenue for investigation of genes involved in estrogen signaling pathways related to sexually dimorphic brain development and their relationship to gender dysphoria.
We report a genomic and phenotypic delineation for two chromosome regions with candidate genes for syndromic intellectual disability at 12q12 and Xp22.31, segregating independently in one family with four affected members. Fine mapping of three affected members, along with six unreported small informative CNVs, narrowed down the candidate chromosomal interval to one gene LRRK2 at 12q12. Expression studies revealed high levels of LRRK2 transcripts in the whole human brain, cerebral cortex and hippocampus. RT-qPCR assays revealed that LRRK2 transcripts were dramatically reduced in our microdeletion patient DGDP289A compared to his healthy grandfather with no deletion. The decreased expression of LRRK2 may affect protein–protein interactions between LRRK2 and its binding partners, of which eight have previously been linked to intellectual disability. These findings corroborate with a role for LRRK2 in cognitive development, and, thus, we propose that intellectual disability and autism, displayed in the 12q12 microdeletions, are likely caused by LRRK2. Using another affected member, DGDP289B, with a microdeletion at Xp22.31, in this family, we performed the genomic and clinical delineation with six published and nine unreported cases. We propose HDHD1 and PNPLA4 for X-linked intellectual disability in this region, since their high transcript levels in the human brain substantiate their role in intellectual functioning.
The portable bladder scanner accurately measures PVR in patients with pelvic organ prolapse and could be considered as an alternative to catheterized assessment. However, stage III/IV prolapse is associated with increased bladder scanner error, which should be considered when determining appropriate candidates for bladder scanner PVR assessment.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Background
Gender expansive and transgender (GET) healthcare extends beyond gender-affirming therapies, reaching every medical specialty and subspecialty. As the number of GET patients seeking health services has increased, so has the need for standards of care regarding GET-affirmative practices throughout the healthcare system. As such, the number of publications surrounding GET-affirmative practices has steadily risen. However, even as such research has gained ground in other areas, one realm in which there has been a relative lag is genetics and genomics (GG).
Content
In this article, we track the GET patient and their laboratory sample from the clinic to the GG laboratory and back. Throughout the preanalytical, analytical, and postanalytical phases, we identify publications, recommendations, and guidelines relevant to the care of the GET community. We also identity knowledge gaps in each area and provide recommendations for affirmative and inclusive processes for addressing those gaps.
Summary
We have identified the practices involved in GG services that would benefit from GET-affirmative process improvement, reviewing relevant affirmative guidelines. Where guidelines could not be found, we identified those knowledge gaps and suggested potential solutions and future directions for implementing GET-affirmative practices.
Subjects completed validated questionnaires, including incontinence [International Consultation on Incontinence QuestionnaireeUrinary Incontinence (ICIQ-UI), Incontinence Resource Use Questionnaire (IRUQ)] and physical activity surveys [Physical Activity Scale for the Elderly (PASE) questionnaire]. Weekly pad usage was determined from the IRUQ. Physical activity was also directly recorded by accelerometer for one week. We examined UI severity (measured by ICIQ or number of pads used) in women with high versus low levels of physical activity and sedentary time using t-test and Wilcoxon rank sum. Linear regression was used to examine relationships between activity measurements and incontinence severity. Spearman's correlation was used to test associations between accelerometer and questionnaire data. RESULTS: Thirty-six subjects were included. Both accelerometer and physical activity questionnaires revealed high prevalence of sedentary behavior and low levels of physical activity in this population. Overall 89% of subjects were highly sedentary. Active time was mostly spent in light intensity activities. Compared to subjects in the 25 th quartile, those in 75 th quartile for moderate and vigorous physical activity duration, step counts, and daily MET rate (measured by accelerometer) had significantly less pad use (p¼0.03, 0.004, and 0.04, respectively). There was a non-significant trend towards greater pad use in those with higher sedentary bout time (p¼0.058). Urinary incontinence scores were not significantly different in women with high versus low physical activity and sedentary bout time (p>0.05). Greater daily step counts and increased total time spent in any level of activity was associated with decreasing pad use (p¼0.045). When comparing accelerometer to physical activity questionnaire, there was no correlation in measures of sedentary or active behavior between the two methods. CONCLUSION: Increased physical activity was significantly associated with decreased use of pads for UI. Sedentary activity showed a nonsignificant trend towards greater pad use. Intervention for UI may be beneficial for increasing physical activity in older adults. The physical activity questionnaire correlated poorly with accelerometer data and likely captures a separate construct of physical activity.
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