Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1

<p>Abstract</p> <p>Background</p> <p>Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in <it>KIF21A</it>. <it>KIF21A </it>encodes a kinesin motor involved in anterograde axonal transport, and the familial and <it>de novo </it>mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of <it>KIF21A </it>mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in <it>KIF21A</it>.</p> <p>Results</p> <p>Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported <it>de novo </it>KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in <it>KIF21A</it>; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands.</p> <p>Conclusion</p> <p>Analysis of sixteen CFEOM1 probands revealed three novel <it>KIF21A </it>mutations and confirmed three reported mutations, bringing the total number of reported <it>KIF21A </it>mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.</p

Comparison of text messaging data collection vs face-to-face interviews for public health surveys:a cluster randomized crossover study of care-seeking for childhood pneumonia and diarrhoea in rural China

Background To compare text messaging and face-to-face interviews to conduct a survey on childhood diarrhoea and pneumonia. Methods Caregivers of young children able to send text messages in Zhao County in rural China were included in this crossover study. Villages (clusters) were randomized into two groups using the ratio 1:1.6 to account for an expected higher drop-out in group 2. In group 1, participants first completed the face-to-face and then text messaging survey; this order was reversed in group 2. We determined data equivalence of 17 questions that were answered by participants who were the same person in both surveys. For the text messaging survey, we assessed the overall and item response rate. Results We included 1014 participants between 16 and 28 March 2013: 371 in 15 villages in group 1 and 643 in 27 villages in group 2. A total of 662 (65.3%) out of 1014 participants responded (first text message question) and a significantly higher proportion who did not respond were from rural areas (P = 0.005). Of 651 participants willing to participate, 356 (54.7%) completed the text messaging survey, which was marginally significantly different between the groups (P = 0.05). In total, 409 participants took part in both surveys: 183 in group 1 and 226 in group 2. There was a significantly higher proportion of caregivers from rural areas in Zhao County in the non-responder group compared to the responder group (P = 0.004). Kappas were substantial for six (0.61–0.80), moderate for two (0.58 and 0.60), and fair for three questions (0.31, 0.35 and 0.37). The proportion of agreement was >90% for five questions; 80.0%-90.0% for five questions; 70.0%, 65.0% and 45.5%. The remaining questions had too small numbers to calculate these values. Conclusions This study shows that text messaging data collection produces data similar to data from face-to-face interviews in a middle-income setting, but the response rate was insufficient for use in public health surveys. Improving the response rate is important, because text message surveys could be of greater value in rural remote areas due to the cost-saving potential

Changes in high-risk sexual behavior, HIV and other STI testing, and PrEP use during the COVID-19 pandemic in a longitudinal cohort of adolescent men who have sex with men 13 to 18 years old in the United States.

The COVID-19 pandemic has disrupted sexual health services among those most vulnerable to HIV acquisition, such as adolescent men who have sex with men (AMSM). We sought to characterize the changes in sexual-risk behaviors, HIV and other STI testing, and pre-exposure prophylaxis (PrEP) use among a longitudinal cohort of AMSM aged 13 to 18 years before and during the COVID-19 pandemic. We observed a significant decline in HIV testing and a marginal decrease in other STI testing since the pandemic began in March 2020. Outreach efforts and innovative remote delivery of sexual health services are needed to support access to healthcare services among AMSM as the pandemic persists

Homonegative Victimization and Perceived Stress among Adolescent Sexual Minority Males: The Attenuating Role of Peer and Family Support.

PURPOSE: Research suggests social support may protect sexual minorities from the harmful effects of victimization that undermine mental and sexual health wellness; however, this relationship has been underexplored among a diverse youth population. We examined the association between lifetime homonegative victimization, perceived stress in the last month, and resilience factors among a diverse sample of adolescent sexual minority males. METHODS: Data were collected between June 2018 and April 2020 as part of the MyPEEPS Mobile study, a multi-site randomized controlled trial evaluating the effectiveness of a mobile behavioral HIV prevention intervention for adolescents living in the U.S. We analyzed baseline survey data from 542 sexual minority males, aged 13-18 years. We used bivariate analyses to examine relationships among variables and multivariable linear regression models to determine if resilience factors attenuated the association between homonegative victimization and perceived stress. RESULTS: Perceived stress was positively associated with younger age, internalized homophobia, experiencing verbal victimization, threats of being outed, and threats of physical violence. Relying on online friends for support and having good family relations both attenuated the relationship between verbal victimization and perceived stress. However, neither of these resilience factors significantly weakened the associations between perceived stress, threats of physical violence, and being outed. CONCLUSION: Resilience factors, including peer and family support, may play an attenuating role in the relationship between homonegative victimization and perceived stress among adolescent sexual minority males