Ethno-racial variations in mental health symptoms among sexually-active gay, bisexual, and other men who have sex with men in Vancouver, Canada: a longitudinal analysis.

BACKGROUND: Minority stress from racism and heterosexism may uniquely interact to impact the mental health of racialized sexual minorities. We examined variations in anxiety and depressive symptoms by reported by ethno-racial identity among gay, bisexual, and other men who have sex with men (gbMSM) in Vancouver, Canada. METHODS: We recruited gbMSM aged ≥ 16 years from February 2012 to February 2015 using respondent-driven sampling (RDS). Participants completed computer assisted self-interviews (CASI) at enrollment and every 6 months until February 2017. We examined factors associated with moderate/severe anxiety and depression scores (> 10) on the Hospital Anxiety and Depression Scale (HADS) and differences in key explanatory variables including sociodemographic, psychosocial, and substance use factors. We used multivariable mixed effects models to assess whether moderate/severe scores were associated with ethno-racial identity across all visits. RESULTS: After RDS-adjustment, of 774 participants, 79.9% of participants identified as gay. 68.6% identified as white, 9.2% as Asian, 9.8% as Indigenous, 7.3% as Latin American, and 5.1% as other ethno-racial identities. Participants contributed a median of 6 follow-up visits (Q1-Q3: 4-7). In the multivariable analysis, Asian participants had decreased odds of moderate/severe anxiety scores compared to white participants (aOR = 0.39; 95% CI: 0.18-0.86), and Latin American participants had decreased odds of moderate/severe depression scores compared to both white (aOR = 0.17; 95% CI: 0.08-0.36) and Asian (aOR = 0.07; 95% CI: 0.02-0.20) participants. CONCLUSION: Asian and Latino gbMSM reported decreased mental health symptoms compared to white participants. Asian and Latino gbMSM in Vancouver appear to manage multiple minority stressors without adversely affecting their mental health.

Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling.

The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.

Search for a gene responsible for Floating-Harbor syndrome on chromosome 12q15q21.1.

Floating-Harbor syndrome (FHS) is characterized by characteristic facial dysmorphism, short stature with delayed bone age, and expressive language delay. To date, the gene(s) responsible for FHS is (are) unknown and the diagnosis is only made on the basis of the clinical phenotype. The majority of cases appeared to be sporadic but rare cases following autosomal dominant inheritance have been reported. We identified a 4.7 Mb de novo 12q15-q21.1 microdeletion in a patient with FHS and intellectual deficiency. Pangenomic 244K array-CGH performed in a series of 12 patients with FHS failed to identify overlapping deletions. We hypothesized that FHS is caused by haploinsufficiency of one of the 19 genes or predictions located in the deletion found in our index patient. Since none of them appeared to be good candidate gene by their function, a high-throughput sequencing approach of the region of interest was used in eight FHS patients. No pathogenic mutation was found in these patients. This approach failed to identify the gene responsible for FHS, and this can be explained by at least four reasons: (i) our index patient could be a phenocopy of FHS; (ii) the disease may be clinically heterogeneous (since the diagnosis relies exclusively on clinical features), (iii) these could be genetic heterogeneity of the disease, (iv) the patient could carry a mutation in a gene located elsewhere. Recent descriptions of patients with 12q15-q21.1 microdeletions argue in favor of the phenocopy hypothesis.