المؤلفون: Ziaei, Amin, Lavery, Amy M, Shao, Xiaorong MA, Adams, Cameron, Casper, T Charles, Rose, John, Candee, Meghan, Weinstock-Guttman, Bianca, Aaen, Greg, Harris, Yolanda, Graves, Jennifer, Benson, Leslie, Gorman, Mark, Rensel, Mary, Mar, Soe, Lotze, Tim, Greenberg, Benjamin, Chitnis, Tanuja, Hart, Janace, Waldman, Amy T, Barcellos, Lisa F, Waubant, Emmanuelle

المصدر: Multiple Sclerosis Journal. 28(9)

مصطلحات موضوعية: Autoimmune Disease, Genetics, Multiple Sclerosis, Brain Disorders, Neurosciences, Neurodegenerative, Climate-Related Exposures and Conditions, Pediatric, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, B7-2 Antigen, Child, Gene-Environment Interaction, Genetic Predisposition to Disease, Genotype, HLA-DRB1 Chains, Humans, Ozone, Risk Factors, Pediatric onset, multiple sclerosis, ozone pollution, gene-environment interaction, CD86, DRB1*15, gene–environment interaction, Clinical Sciences, Neurology & Neurosurgery

الوصف: BackgroundWe previously reported a relationship between air pollutants and increased risk of pediatric-onset multiple sclerosis (POMS). Ozone is an air pollutant that may play a role in multiple sclerosis (MS) pathoetiology. CD86 is the only non-HLA gene associated with POMS for which expression on antigen-presenting cells (APCs) is changed in response to ozone exposure.ObjectivesTo examine the association between county-level ozone and POMS, and the interactions between ozone pollution, CD86, and HLA-DRB1*15, the strongest genetic variant associated with POMS.MethodsCases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. County-level-modeled ozone data were acquired from the CDC's Environmental Tracking Network. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS was assessed by logistic regression. Interactions between tertiles of ozone level and the GG genotype of the rs928264 (G/A) single nucleotide polymorphism (SNP) within CD86, and the presence of DRB1*15:01 (DRB1*15) on odds of POMS were evaluated. Models were adjusted for age, sex, genetic ancestry, and mother's education. Additive interaction was estimated using relative excess risk due to interaction (RERI) and attributable proportions (APs) of disease were calculated.ResultsA total of 334 POMS cases and 565 controls contributed to the analyses. County-level ozone was associated with increased odds of POMS (odds ratio 2.47, 95% confidence interval (CI): 1.69-3.59 and 1.95, 95% CI: 1.32-2.88 for the upper two tertiles, respectively, compared with the lowest tertile). There was a significant additive interaction between high ozone tertiles and presence of DRB1*15, with a RERI of 2.21 (95% CI: 0.83-3.59) and an AP of 0.56 (95% CI: 0.33-0.79). Additive interaction between high ozone tertiles and the CD86 GG genotype was present, with a RERI of 1.60 (95% CI: 0.14-3.06) and an AP of 0.37 (95% CI: 0.001-0.75) compared to the lowest ozone tertile. AP results indicated that approximately half of the POMS risk in subjects can be attributed to the possible interaction between higher county-level ozone carrying either DRB1*15 or the CD86 GG genotype.ConclusionsIn addition to the association between high county-level ozone and POMS, we report evidence for additive interactions between higher county-level ozone and DRB1*15 and the CD86 GG genotype. Identifying gene-environment interactions may provide mechanistic insight of biological processes at play in MS susceptibility. Our work suggests a possible role of APCs for county-level ozone-induced POMS risk.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4bh586rrTest

المؤلفون: Sebastian, Cherbuin, Nicolas, Barcellos, Lisa F, Roalstad, Shelly, Casper, Charles, Hart, Janace, Aaen, Gregory S, Krupp, Lauren, Benson, Leslie, Gorman, Mark, Candee, Meghan, Chitnis, Tanuja, Goyal, Manu, Greenberg, Benjamin, Mar, Soe, Rodriguez, Moses, Rubin, Jennifer, Schreiner, Teri, Waldman, Amy, Weinstock-Guttman, Bianca, Graves, Jennifer, Waubant, Emmanuelle, Lucas, Robyn, Centers, on behalf of US Network of Pediatric Multiple Sclerosis

المصدر: Neurology. 98(3)

مصطلحات موضوعية: Neurosciences, Neurodegenerative, Pediatric, Prevention, Autoimmune Disease, Multiple Sclerosis, Brain Disorders, Clinical Research, 2.2 Factors relating to the physical environment, Aetiology, Good Health and Well Being, Child, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Humans, Risk Factors, Sunlight, Ultraviolet Rays, United States, US Network of Pediatric Multiple Sclerosis Centers, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery

الوصف: Background and objectivesThis study aims to determine the contributions of sun exposure and ultraviolet radiation (UVR) exposure to risk of pediatric-onset multiple sclerosis (MS).MethodsChildren with MS and controls recruited from multiple centers in the United States were matched on sex and age. Multivariable conditional logistic regression was used to investigate the association of time spent outdoors daily in summer, use of sun protection, and ambient summer UVR dose in the year before birth and the year before diagnosis with MS risk, with adjustment for sex, age, race, birth season, child's skin color, mother's education, tobacco smoke exposure, being overweight, and Epstein-Barr virus infection.ResultsThree hundred thirty-two children with MS (median disease duration 7.3 months) and 534 controls were included after matching on sex and age. In a fully adjusted model, compared to spending

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2s32h2dbTest

المؤلفون: Greenberg, Benjamin M, Casper, Theron Charles, Mar, Soe S, Ness, Jayne M, Plumb, Patricia, Liang, Shannon, Goyal, Manu, Weinstock-Guttman, Bianca, Rodriguez, Moses, Aaen, Gregory S, Belman, Anita, Barcellos, Lisa F, Rose, John W, Gorman, Mark P, Benson, Leslie A, Candee, Meghan, Chitnis, Tanuja, Harris, Yolanda C, Kahn, Ilana L, Roalstad, Shelly, Hart, Janace, Lotze, Timothy E, Rensel, Mary, Rubin, Jennifer P, Schreiner, Teri L, Tillema, Jan-Mendelt, Waldman, Amy Tara, Krupp, Lauren, Graves, Jennifer, Drake, Kaylea, Waubant, Emmanuelle

المصدر: Neurology(R) neuroimmunology & neuroinflammation. 8(5)

مصطلحات موضوعية: Neurosciences, Clinical Research, Neurodegenerative, Genetics, Autoimmune Disease, Multiple Sclerosis, Brain Disorders, Pediatric, 2.1 Biological and endogenous factors, 2.4 Surveillance and distribution, 7.1 Individual care needs, Neurological

الوصف: Background and objectiveThe objective of this study was to determine whether family members of patients with pediatric multiple sclerosis (MS) have an increased prevalence of autoimmune conditions compared with controls.MethodsData collected during a pediatric MS case-control study of risk factors included information about various autoimmune diseases in family members. The frequency of these disorders was compared between cases and controls.ResultsThere was an increased rate of autoimmune diseases among family members of pediatric MS cases compared with controls with first-degree history of MS excluded (OR = 2.27, 95% CI 1.71-3.01, p < 0.001). There was an increased rate of MS among second-degree relatives of pediatric MS cases compared with controls (OR = 3.47, 95% CI 1.36-8.86, p = 0.009). The OR for MS was 2.64 when restricted to maternal relatives and 6.37 when restricted to paternal relatives.DiscussionThe increased rates of autoimmune disorders, including thyroid disorders and MS among families of patients with pediatric MS, suggest shared genetic factors among families with children diagnosed with pediatric MS.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9zz0n3hnTest

المؤلفون: Rhead, Brooke, Shao, Xiaorong, Graves, Jennifer S, Chitnis, Tanuja, Waldman, Amy T, Lotze, Timothy, Schreiner, Teri, Belman, Anita, Krupp, Lauren, Greenberg, Benjamin M, Weinstock–Guttman, Bianca, Aaen, Gregory, Tillema, Jan M, Rodriguez, Moses, Hart, Janace, Caillier, Stacy, Ness, Jayne, Harris, Yolanda, Rubin, Jennifer, Candee, Meghan S, Gorman, Mark, Benson, Leslie, Mar, Soe, Kahn, Ilana, Rose, John, Casper, T Charles, Quach, Hong, Quach, Diana, Schaefer, Catherine, Waubant, Emmanuelle, Barcellos, Lisa F, Centers, Network of Pediatric MS

المصدر: Annals of Clinical and Translational Neurology. 6(6)

مصطلحات موضوعية: Clinical and Health Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Biotechnology, Genetics, Pediatric, Multiple Sclerosis, Neurodegenerative, Brain Disorders, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adolescent, Binding Sites, Biomarkers, California, Child, Female, Gene Expression Profiling, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Male, MicroRNAs, Polymorphism, Single Nucleotide, Signal Transduction, US Network of Pediatric MS Centers, Clinical Sciences, Clinical and health psychology

الوصف: ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2ts502k9Test

المؤلفون: Chi, Calvin, Shao, Xiaorong, Rhead, Brooke, Gonzales, Edlin, Smith, Jessica B, Xiang, Anny H, Graves, Jennifer, Waldman, Amy, Lotze, Timothy, Schreiner, Teri, Weinstock-Guttman, Bianca, Aaen, Gregory, Tillema, Jan-Mendelt, Ness, Jayne, Candee, Meghan, Krupp, Lauren, Gorman, Mark, Benson, Leslie, Chitnis, Tanuja, Mar, Soe, Belman, Anita, Casper, Theron Charles, Rose, John, Moodley, Manikum, Rensel, Mary, Rodriguez, Moses, Greenberg, Benjamin, Kahn, Llana, Rubin, Jennifer, Schaefer, Catherine, Waubant, Emmanuelle, Langer-Gould, Annette, Barcellos, Lisa F

المصدر: PLoS genetics. 15(1)

مصطلحات موضوعية: Humans, Multiple Sclerosis, Genetic Predisposition to Disease, Transcription Factors, HLA-A3 Antigen, HLA-B7 Antigen, Haplotypes, Polymorphism, Single Nucleotide, Alleles, African Americans, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, HLA-DRB1 Chains, Polymorphism, Single Nucleotide, Genetics, Developmental Biology

الوصف: Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors. We characterized the ancestry of MS-associated alleles using RFMix, a conditional random field parameterized by random forests, to estimate their local ancestry in the largest assembled admixed population to date, with 3,692 African Americans, 4,915 Asian Americans, and 3,777 Hispanics. The majority of MS-associated human leukocyte antigen (HLA) alleles, including the prominent HLA-DRB1*15:01 risk allele, exhibited cosmopolitan ancestry. Ancestry-specific MS-associated HLA alleles were also identified. Analysis of the HLA-DRB1*15:01 risk allele in African Americans revealed that alleles on the European haplotype conferred three times the disease risk compared to those on the African haplotype. Furthermore, we found evidence that the European and African HLA-DRB1*15:01 alleles exhibit single nucleotide polymorphism (SNP) differences in regions encoding the HLA-DRB1 antigen-binding heterodimer. Additional evidence for increased risk of MS conferred by the European haplotype were found for HLA-B*07:02 and HLA-A*03:01 in African Americans. Most of the 200 non-HLA MS SNPs previously established in European populations were not significantly associated with MS in admixed populations, nor were they ancestrally more European in cases compared to controls. Lastly, a genome-wide search of association between European ancestry and MS revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. In conclusion, our study established that the genetic ancestry of MS-associated alleles is complex and implicated that difference in MS prevalence could be explained by the ancestry of MS-associated alleles.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2g87454hTest

المؤلفون: Mar, Soe, Liang, Shannon, Waltz, Michael, Casper, T Charles, Goyal, Manu, Greenberg, Benjamin, Weinstock‐Guttman, Bianca, Rodriguez, Moses, Aaen, Gregory, Belman, Anita, Barcellos, Lisa F, Rose, John, Gorman, Mark, Benson, Leslie, Candee, Meghan, Chitnis, Tanjua, Harris, Yolanda, Kahn, Ilana, Roalsted, Shelly, Hart, Janace, Lotze, Timothy, Moodley, Manikum, Ness, Jayne, Rensel, Mary, Rubin, Jennifer, Schreiner, Teri, Tillema, Jan‐Mendelt, Waldman, Amy, Krupp, Lauren, Graves, Jennifer S, Waubant, Emmanuelle, Centers, the US Network of Pediatric Multiple Sclerosis

المصدر: Annals of Clinical and Translational Neurology. 5(12)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Neurosciences, Multiple Sclerosis, Autoimmune Disease, Brain Disorders, Prevention, Pediatric, Pediatric Cancer, Cancer, Neurodegenerative, Clinical Research, Neurological, U.S. Network of Pediatric Multiple Sclerosis Centers, Clinical Sciences, Clinical and health psychology

الوصف: BackgroundThere is limited information about the potential associations of multiple sclerosis (MS) and commonly used household chemicals.MethodsWe performed a case-control study of exposures to common household chemicals during childhood in children with MS and healthy pediatric controls. Exposures to household products were collected from a comprehensive questionnaire (http://www.usnpmsc.org/Documents/EnvironmentalAssessment.pdfTest) completed by parents at the time of enrollment in the study. Cases included children diagnosed with MS or clinically isolated syndrome with at least two silent T2 bright lesions on MRI, recruited within 4 years of disease onset from 16 pediatric MS clinics in the USA. Multivariate analyses using logistic regression were adjusted for possible confounders including age, sex, race, ethnicity, mother's highest level of education, and urban versus rural living.ResultsQuestionnaire responses to household chemicals were available for 312 eligible cases (median age 15.7 years, 63% girls) and 490 healthy controls (median age 15.0, 57% girls). Exposure to rodenticides (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.35-3.26, P ≤ 0.001), weed control agents (OR 1.99, 95% CI 1.36-2.92, P ≤ 0.001) and products for plant/tree disease control (OR 2.72, 95% CI 1.54-4.82, P ≤ 0.001) anytime during childhood were associated with an increased risk for pediatric-onset MS in adjusted and multiple comparisons analyses.ConclusionsOur findings suggest that exposure to specific household chemicals during early childhood is associated with the risk of developing pediatric-onset MS. Future studies are needed to elucidate a causal relationship and the exact agents involved.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/57m27381Test

المؤلفون: Gianfrancesco, Milena A, Stridh, Pernilla, Shao, Xiaorong, Rhead, Brooke, Graves, Jennifer S, Chitnis, Tanuja, Waldman, Amy, Lotze, Timothy, Schreiner, Teri, Belman, Anita, Greenberg, Benjamin, Weinstock-Guttman, Bianca, Aaen, Gregory, Tillema, Jan M, Hart, Janace, Caillier, Stacy, Ness, Jayne, Harris, Yolanda, Rubin, Jennifer, Candee, Meghan, Krupp, Lauren, Gorman, Mark, Benson, Leslie, Rodriguez, Moses, Mar, Soe, Kahn, Ilana, Rose, John, Roalstad, Shelly, Casper, T Charles, Shen, Ling, Quach, Hong, Quach, Diana, Hillert, Jan, Hedstrom, Anna, Olsson, Tomas, Kockum, Ingrid, Alfredsson, Lars, Schaefer, Catherine, Barcellos, Lisa F, Waubant, Emmanuelle, Network of Pediatric Multiple Sclerosis Centers

المصدر: Multiple sclerosis (Houndmills, Basingstoke, England). 24(14)

مصطلحات موضوعية: Network of Pediatric Multiple Sclerosis Centers, Humans, Multiple Sclerosis, Genetic Predisposition to Disease, Logistic Models, Risk Factors, Polymorphism, Single Nucleotide, Sweden, Female, Male, Genetic Testing, HLA-DRB1 Chains, Multiple sclerosis, epidemiology, genetics, pediatrics, Brain Disorders, Human Genome, Autoimmune Disease, Genetics, Prevention, Neurosciences, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Clinical Sciences, Neurology & Neurosurgery

الوصف: BackgroundStrong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology.ObjectiveWe comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS.MethodsCases with onset

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/33c4m6r5Test

المؤلفون: Nourbakhsh, Bardia, Rutatangwa, Alice, Waltz, Michael, Rensel, Mary, Moodley, Manikum, Graves, Jennifer, Casper, Theron, Waldman, Amy, Belman, Anita, Greenberg, Benjamin, Goyal, Manu, Harris, Yolanda, Kahn, Ilana, Lotze, Timothy, Mar, Soe, Schreiner, Teri, Aaen, Gregory, Hart, Janace, Ness, Jayne, Rubin, Jennifer, Tillema, Jan-Mendelt, Krupp, Lauren, Gorman, Mark, Benson, Leslie, Rodriguez, Moses, Chitnis, Tanuja, Rose, John, Candee, Meghan, Weinstock-Guttman, Bianca, Shao, Xiaorong, Barcellos, Lisa, James, Judith, Waubant, Emmanuelle

المصدر: Annals of Clinical and Translational Neurology. 5(10)

الوصف: OBJECTIVE: While prior Epstein-Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility to pediatric MS and if there are interactions between genetic and demographic factors and viral infections. METHODS: Cases with pediatric-onset MS or clinically isolated syndrome within 4 years of disease onset, and controls were recruited from 16 American pediatric MS centers. Logistic regression models adjusted for potential confounders assessed the association between case status and serological evidence for past infection with EBV, cytomegalovirus (CMV), Herpes Simplex viruses-1 (HSV-1) and -2. We determined the heterogeneity of the effect of viral infection on the risk of having MS according to race, ethnicity and HLA-DRB1:1501 status. RESULTS: A total of 356 pediatric cases and 493 controls were recruited. In multivariable models, EBV-viral capsid antigen (VCA) seropositivity was associated with increased odds of having MS by 7.4 times (95% CI: 4.5-12.0, P < 0.001). Seropositivity for HSV-1 was also associated with increased odds of having MS (OR 1.54, 95% CI: 1.06-2.25, P = 0.025) but this increase was seen only in Whites (OR = 2.18, 95% CI 1.35-3.52, P < 0.001) and those negative for HLA-DRB1*1501 (OR = 1.89, 95% CI 1.17-3.03, P = 0.009). The effect of remote EBV infection on the risk of pediatric MS depended on race and HLA-DRB1*15:01 status. INTERPRETATION: EBV seropositivity is strongly associated with pediatric MS, as is HSV-1 seropositivity in subjects negative for HLA-DRB1*15:01. Our report of interactions between select viral exposures, and age, race and DRB1 status suggests a complex effect of environmental and genetic risk factors on MS development.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3022t2x8Test

المؤلفون: McKnight, Dianalee, Morales, Ana, Hatchell, Kathryn E, Bristow, Sara L, Bonkowsky, Joshua L, Perry, Michael Scott, Berg, Anne T, Borlot, Felippe, Esplin, Edward D, Moretz, Chad, Angione, Katie, Ríos-Pohl, Loreto, Nussbaum, Robert L, Aradhya, Swaroop, Haldeman-Englert, Chad R, Levy, Rebecca J, Parachuri, Venu G, Lay-Son, Guillermo, de Montellano, David J Dávila-Ortiz, Ramirez-Garcia, Miguel Angel, Benítez Alonso, Edmar O, Ziobro, Julie, Chirita-Emandi, Adela, Felix, Temis M, Kulasa-Luke, Dianne, Megarbane, Andre, Karkare, Shefali, Chagnon, Sarah L, Humberson, Jennifer B, Assaf, Melissa J, Silva, Sebastian, Zarroli, Katherine, Boyarchuk, Oksana, Nelson, Gary R, Palmquist, Rachel, Hammond, Katherine C, Hwang, Sean T, Boutlier, Susan B, Nolan, Melinda, Batley, Kaitlin Y, Chavda, Devraj, Reyes-Silva, Carlos Alberto, Miroshnikov, Oleksandr, Zuccarelli, Britton, Amlie-Wolf, Louise, Wheless, James W, Seinfeld, Syndi, Kanhangad, Manoj, Freeman, Jeremy L, Monroy-Santoyo, Susana, Rodriguez-Vazquez, Natalia, Ryan, Monique M, Machie, Michelle, Guerra, Patricio, Hassan, Muhammad Jawad, Candee, Meghan S, Bupp, Caleb P, Park, Kristen L, Muller, Eric, Lupo, Pamela, Pedersen, Robert C, Arain, Amir M, Murphy, Andrea, Schatz, Krista, Mu, Weiyi, Kalika, Paige M, Plaza, Lautaro, Kellogg, Marissa A, Lora, Evelyn G, Carson, Robert P, Svystilnyk, Victoria, Venegas, Viviana, Luke, Rebecca R, Jiang, Huiyuan, Stetsenko, Tetiana, Dueñas-Roque, Milagros M, Trasmonte, Joseph, Burke, Rebecca J, Hurst, Anna C E, Smith, Douglas M, Massingham, Lauren J, Pisani, Laura, Costin, Carrie E, Ostrander, Betsy, Filloux, Francis M, Ananth, Amitha L, Mohamed, Ismail S, Nechai, Alla, Dao, Jasmin M, Fahey, Michael C, Aliu, Ermal, Falchek, Stephen, Press, Craig A, Treat, Lauren, Eschbach, Krista, Starks, Angela, Kammeyer, Ryan, Bear, Joshua J, Jacobson, Mona, Chernuha, Veronika, Meibos, Bailey, Wong, Kristen, Sweney, Matthew T, Espinoza, A Chris, Van Orman, Colin B, Weinstock, Arie, Kumar, Ashutosh, Soler-Alfonso, Claudia, Nolan, Danielle A, Raza, Muhammad, Rojas Carrion, Miguel David, Chari, Geetha, Marsh, Eric D, Shiloh-Malawsky, Yael, Parikh, Sumit, Gonzalez-Giraldo, Ernesto, Fulton, Stephen, Sogawa, Yoshimi, Burns, Kaitlyn, Malets, Myroslava, Montiel Blanco, Johnny David, Habela, Christa W, Wilson, Carey A, Guzmán, Guillermo G, Pavliuk, Mariia

المصدر: JAMA neurology ; 79 ; 12 ; 1267 ; 1276 ; United States

الوصف: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. ; To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. ; This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. ; Genetic test results. ; Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. ; Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of ...

العلاقة: https://jamanetwork.com/journals/jamaneurology/fullarticle/2797510Test; McKnight D, Morales A, Hatchell KE, Bristow SL, Bonkowsky JL, Perry MS, Berg AT, Borlot F, Esplin ED, Moretz C, Angione K, Ríos-Pohl L, Nussbaum RL, Aradhya S; ELEVIATE Consortium; Haldeman-Englert CR, Levy RJ, Parachuri VG, Lay-Son G, de Montellano DJD, Ramirez-Garcia MA, Benítez Alonso EO, Ziobro J, Chirita-Emandi A, Felix TM, Kulasa-Luke D, Megarbane A, Karkare S, Chagnon SL, Humberson JB, Assaf MJ, Silva S, Zarroli K, Boyarchuk O, Nelson GR, Palmquist R, Hammond KC, Hwang ST, Boutlier SB, Nolan M, Batley KY, Chavda D, Reyes-Silva CA, Miroshnikov O, Zuccarelli B, Amlie-Wolf L, Wheless JW, Seinfeld S, Kanhangad M, Freeman JL, Monroy-Santoyo S, Rodriguez-Vazquez N, Ryan MM, Machie M, Guerra P, Hassan MJ, Candee MS, Bupp CP, Park KL, Muller E 2nd, Lupo P, Pedersen RC, Arain AM, Murphy A, Schatz K, Mu W, Kalika PM, Plaza L, Kellogg MA, Lora EG, Carson RP, Svystilnyk V, Venegas V, Luke RR, Jiang H, Stetsenko T, Dueñas-Roque MM, Trasmonte J, Burke RJ, Hurst ACE, Smith DM, Massingham LJ, Pisani L, Costin CE, Ostrander B, Filloux FM, Ananth AL, Mohamed IS, Nechai A, Dao JM, Fahey MC, Aliu E, Falchek S, Press CA, Treat L, Eschbach K, Starks A, Kammeyer R, Bear JJ, Jacobson M, Chernuha V, Meibos B, Wong K, Sweney MT, Espinoza AC, Van Orman CB, Weinstock A, Kumar A, Soler-Alfonso C, Nolan DA, Raza M, Rojas Carrion MD, Chari G, Marsh ED, Shiloh-Malawsky Y, Parikh S, Gonzalez-Giraldo E, Fulton S, Sogawa Y, Burns K, Malets M, Montiel Blanco JD, Habela CW, Wilson CA, Guzmán GG, Pavliuk M. Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice. JAMA Neurol. 2022 Dec 1;79(12):1267-1276. doi:10.1001/jamaneurol.2022.3651. PMID: 36315135; PMCID: PMC9623482.; http://hdl.handle.net/20.500.12648/8109Test; JAMA neurology

الإتاحة: https://doi.org/20.500.12648/8109Test
https://doi.org/10.1001/jamaneurol.2022.3651Test
https://hdl.handle.net/20.500.12648/8109Test

المؤلفون: Carey, John, Jaspersen, Sue, Candee, Meghan, Battaglia, Agatino, Bruns, Deborah, Fishler, Kristen

المصدر: Genetics in Medicine Open ; volume 1, issue 1, page 100168 ; ISSN 2949-7744

الإتاحة: https://doi.org/10.1016/j.gimo.2023.100168Test
https://api.elsevier.com/content/article/PII:S2949774423001681?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2949774423001681?httpAccept=text/plainTest