This article reports a study of the function and composition of social support networks among diverse lesbian, gay, and bisexual (LGB) men and women (n = 396) in comparison to their heterosexual peers (n = 128). Data were collected using a structured social support network matrix in a community sample recruited in New York City. Our findings show that gay and bisexual men may rely on “chosen families” more than lesbian and bisexual women. Both heterosexuals and LGBs relied less on family and more on other people (e.g., friends, coworkers) for everyday social support (e.g., recreational and social activities, talking about problems). Providers of everyday social support were most often of the same sexual orientation and race/ethnicity as participants. In seeking major support (e.g., borrowing large sums of money), heterosexual men and women along with lesbian and bisexual women relied primarily on their families, but gay and bisexual men relied primarily on other LGB individuals. Racial/ethnic minority LGBs relied on LGB similar others at the same rate as did White LGBs but, notably, racial/ethnic minority LGBs reported receiving fewer dimensions of support. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

One possible approach to prevention of suicide attempts is to encourage help-seeking among individuals at risk. We assessed whether different forms of treatment were associated with lower odds of a suicide attempt in a diverse group of 388 lesbian, gay, and bisexual (LGB) adults aged 18–59, sampled from New York City venues. Of individuals who attempted suicide, 23% sought mental health or medical treatment and 14% sought religious or spiritual treatment prior to the suicide attempt. Black and Latino LGBs were underrepresented in mental health or medical treatment and Black LGBs were overrepresented in religious or spiritual treatment. Seeking mental health or medical treatment was not associated with lower odds of a suicide attempt; seeking religious or spiritual treatment was associated with higher odds of a suicide attempt. We discuss these results and posit hypotheses for further research of this understudied topic.

Mutations in the ABCA4 gene are a common cause of autosomal recessive retinal degeneration. All mouse models to date are based on knockouts of Abca4, even though the disease is often caused by missense mutations such as the complex allele L541P;A1038V (PV). We now show that the PV mutation causes severe human disease whereas the V mutation alone causes mild disease. Mutant ABCA4 proteins expressed heterologously in mammalian cells retained normal cellular localization. However, basal and all-trans-retinal-stimulated ATPase activities were reduced substantially for P and PV but only mildly for V. Electron microscopy revealed marked structural changes and misfolding for the P and PV mutants but few changes for the V mutant, consistent with the disease severity difference in patients. We generated Abca4(PV/PV) knock-in mice homozygous for the complex PV allele to investigate the effects of this misfolding mutation in vivo. Mutant ABCA4 RNA levels approximated WT ABCA4 RNA levels but, surprisingly, only trace amounts of mutant ABCA4 protein were noted in the retina. RNA sequencing of WT, Abca4(-/-) and Abca4(PV/PV) mice revealed mild gene expression alterations in the retina and RPE. Similar to Abca4(-/-) mice, Abca4(PV/PV) mice showed substantial A2E and lipofuscin accumulation in their RPE cells but no retinal degeneration up to 12 months of age. Thus, rapid degradation of this large misfolded mutant protein in mouse retina caused little detectable photoreceptor degeneration. These findings suggest likely differences in the unfolded protein response between murine and human photoreceptors and support development of therapies directed at increasing this capability in patients.

Human X-linked blue-cone monochromacy (BCM), a disabling congenital visual disorder of cone photoreceptors, is a candidate disease for gene augmentation therapy. BCM is caused by either mutations in the red (OPN1LW) and green (OPN1MW) cone photoreceptor opsin gene array or large deletions encompassing portions of the gene array and upstream regulatory sequences that would predict a lack of red or green opsin expression. The fate of opsin-deficient cone cells is unknown. We know that rod opsin null mutant mice show rapid postnatal death of rod photoreceptors. Using in vivo histology with high-resolution retinal imaging, we studied a cohort of 20 BCM patients (age range 5-58) with large deletions in the red/green opsin gene array. Already in the first years of life, retinal structure was not normal: there was partial loss of photoreceptors across the central retina. Remaining cone cells had detectable outer segments that were abnormally shortened. Adaptive optics imaging confirmed the existence of inner segments at a spatial density greater than that expected for the residual blue cones. The evidence indicates that human cones in patients with deletions in the red/green opsin gene array can survive in reduced numbers with limited outer segment material, suggesting potential value of gene therapy for BCM.

Purpose

To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2.

Methods

Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA.

Results

We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region).

Conclusions

This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration.