@article {671, title = {Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0149041}, abstract = {

Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0 x 10(-8)). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3\% vs. 3.9\% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95\% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95\% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95\% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95\% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism.

}, keywords = {Adolescent, Adult, Autism Spectrum Disorder, Child, Child, Preschool, Female, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Humans, Infant, Male, Middle Aged, Mutation, Neoplasms, Oncogenes, Prevalence, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0149041}, author = {Darbro, Benjamin W and Singh, Rohini and Zimmerman, M Bridget and Mahajan, Vinit B and Bassuk, Alexander G} } @article {129, title = {Proteomic analysis of vitreous biopsy techniques.}, journal = {Retina}, volume = {32}, year = {2012}, month = {2012 Nov-Dec}, pages = {2141-9}, abstract = {

PURPOSE: To compare vitreous biopsy methods using analysis platforms used in proteomics biomarker discovery.

METHODS: Vitreous biopsies from 10 eyes were collected sequentially using a 23-gauge needle and a 23-gauge vitreous cutter instrument. Paired specimens were evaluated by UV absorbance spectroscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and liquid chromatography tandem mass spectrometry (LC-MS/MS).

RESULTS: The total protein concentration obtained with a needle and vitrectomy instrument biopsy averaged 1.10 mg/mL (standard error of the mean = 0.35) and 1.13 mg/mL (standard error of the mean = 0.25), respectively. In eight eyes with low or medium viscidity, there was a very high correlation (R = 0.934) between the biopsy methods. When data from 2 eyes with high viscidity vitreous were included, the correlation was reduced (R = 0.704). The molecular weight protein sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles of paired needle and vitreous cutter samples were similar, except for a minority of pairs with single band intensity variance. Using LC-MS/MS, equivalent peptides were identified with similar frequencies (R \≥ 0.90) in paired samples.

CONCLUSION: Proteins and peptides collected from vitreous needle biopsies are nearly equivalent to those obtained from a vitreous cutter instrument. This study suggests both techniques may be used for most proteomic and biomarker discovery studies of vitreoretinal diseases, although a minority of proteins and peptides may differ in concentration.

}, keywords = {Adolescent, Aged, Biological Markers, Biopsy, Chromatography, Liquid, Electrophoresis, Polyacrylamide Gel, Eye Diseases, Eye Proteins, Female, Humans, Male, Middle Aged, Proteomics, Spectrophotometry, Ultraviolet, Tandem Mass Spectrometry, Vitrectomy, Vitreous Body, Young Adult}, author = {Skeie, Jessica M and Brown, Eric N and Martinez, Harryl D and Russell, Stephen R and Birkholz, Emily S and Folk, James C and Boldt, H Culver and Gehrs, Karen M and Stone, Edwin M and Wright, Michael E and Mahajan, Vinit B} } @article {151, title = {Seroreactivity against aqueous-soluble and detergent-soluble retinal proteins in posterior uveitis.}, journal = {Archives of ophthalmology}, volume = {129}, year = {2011}, month = {2011 Apr}, pages = {415-20}, abstract = {

To characterize the seroreactivity against retinal proteins in patients with posterior uveitis, retinal disease of noninflammatory origin, and healthy controls.

}, keywords = {Adolescent, Adult, Autoantibodies, Autoantigens, Blotting, Western, Electrophoresis, Polyacrylamide Gel, Eye Proteins, Female, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Male, Middle Aged, Retina, Retinal Degeneration, Solubility, Uveitis, Posterior, Young Adult}, author = {Ko, Audrey C and Brinton, Jason P and Mahajan, Vinit B and Zimmerman, Bridget and Brinton, Gregory S and Stone, Edwin M and Folk, James C and Mullins, Robert F} } @article {173, title = {A new macular dystrophy with anomalous vascular development, pigment spots, cystic spaces, and neovascularization.}, journal = {Archives of ophthalmology}, volume = {127}, year = {2009}, month = {2009 Nov}, pages = {1449-57}, abstract = {

To clinically phenotype an inherited macular dystrophy with peculiar intraretinal pigment spots, cysts, and hemorrhage in a 24-year-old female proband and her family.

}, keywords = {Adolescent, Adult, Amblyopia, Child, Child, Preschool, Cysts, Electroretinography, Female, Fluorescein Angiography, Humans, Macular Degeneration, Male, Middle Aged, Pedigree, Phenotype, Retinal Hemorrhage, Retinal Neovascularization, Retinal Pigment Epithelium, Retinal Vessels, Strabismus, Tomography, Optical Coherence, Visual Acuity, Young Adult}, author = {Mahajan, Vinit B and Russell, Stephen R and Stone, Edwin M} }