Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers / Caitlin M. HUDAC in Autism Research, 13-8 (August 2020)  

Public ISBD [article]  inAutism Research > 13-8 (August 2020) . - p.1300-1310 Titre : Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers Type de document : texte imprimé Auteurs : Caitlin M. HUDAC, Auteur ; Joanna BOVE, Auteur ; Shelley BARBER, Auteur ; Michael DUYZEND, Auteur ; Ari WALLACE, Auteur ; Christa Lese MARTIN, Auteur ; David H. LEDBETTER, Auteur ; Ellen HANSON, Auteur ; Robin P. GOIN-KOCHEL, Auteur ; LeeAnne GREEN SNYDER, Auteur ; Wendy K. CHUNG, Auteur ; Evan E. EICHLER, Auteur ; Raphael A. BERNIER, Auteur Article en page(s) : p.1300-1310 Langues : Anglais (eng) Mots-clés : 16p11.2 deletion  16p11.2 duplication  adaptive functioning  autism spectrum disorder  cognitive functioning  individual variability/heterogeneity Index. décimale : PER Périodiques Résumé : Individuals with 16p11.2 copy number variant (CNV) show considerable phenotypic heterogeneity. Although autism spectrum disorder (ASD) is reported in approximately 20-23% of individuals with 16p11.2 CNVs, ASD-associated symptoms are observed in those without a clinical ASD diagnosis. Previous work has shown that genetic variation and prenatal and perinatal birth complications influence ASD risk and symptom severity. This study examined the impact of genetic and environmental risk factors on phenotypic heterogeneity among 16p11.2 CNV carriers. Participants included individuals with a 16p11.2 deletion (N = 96) or duplication (N = 77) with exome sequencing from the Simons VIP study. The presence of prenatal factors, perinatal events, additional genetic events, and gender was studied. Regression analyses examined the contribution of each risk factor on ASD symptomatology, cognitive functioning, and adaptive abilities. For deletion carriers, perinatal and additional genetic events were associated with increased ASD symptomatology and decrements in cognitive and adaptive functioning. For duplication carriers, secondary genetic events were associated with greater cognitive impairments. Being female sex was a protective factor for both deletion and duplication carriers. Our findings suggest that ASD-associated risk factors contribute to the variability in symptom presentation in individuals with 16p11.2 CNVs. LAY SUMMARY: There are a wide range of autism spectrum disorder (ASD) symptoms and abilities observed for individuals with genetic changes of the 16p11.2 region. Here, we found perinatal complications contributed to more severe ASD symptoms (deletion carriers) and additional genetic mutations contributed to decreased cognitive abilities (deletion and duplication carriers). A potential protective factor was also observed for females with 16p11.2 variations. Autism Res 2020, 13: 1300-1310. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2332 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430 [article] Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers [texte imprimé] / Caitlin M. HUDAC, Auteur ; Joanna BOVE, Auteur ; Shelley BARBER, Auteur ; Michael DUYZEND, Auteur ; Ari WALLACE, Auteur ; Christa Lese MARTIN, Auteur ; David H. LEDBETTER, Auteur ; Ellen HANSON, Auteur ; Robin P. GOIN-KOCHEL, Auteur ; LeeAnne GREEN SNYDER, Auteur ; Wendy K. CHUNG, Auteur ; Evan E. EICHLER, Auteur ; Raphael A. BERNIER, Auteur . - p.1300-1310. Langues : Anglais (eng) in Autism Research > 13-8 (August 2020) . - p.1300-1310 Mots-clés : 16p11.2 deletion  16p11.2 duplication  adaptive functioning  autism spectrum disorder  cognitive functioning  individual variability/heterogeneity Index. décimale : PER Périodiques Résumé : Individuals with 16p11.2 copy number variant (CNV) show considerable phenotypic heterogeneity. Although autism spectrum disorder (ASD) is reported in approximately 20-23% of individuals with 16p11.2 CNVs, ASD-associated symptoms are observed in those without a clinical ASD diagnosis. Previous work has shown that genetic variation and prenatal and perinatal birth complications influence ASD risk and symptom severity. This study examined the impact of genetic and environmental risk factors on phenotypic heterogeneity among 16p11.2 CNV carriers. Participants included individuals with a 16p11.2 deletion (N = 96) or duplication (N = 77) with exome sequencing from the Simons VIP study. The presence of prenatal factors, perinatal events, additional genetic events, and gender was studied. Regression analyses examined the contribution of each risk factor on ASD symptomatology, cognitive functioning, and adaptive abilities. For deletion carriers, perinatal and additional genetic events were associated with increased ASD symptomatology and decrements in cognitive and adaptive functioning. For duplication carriers, secondary genetic events were associated with greater cognitive impairments. Being female sex was a protective factor for both deletion and duplication carriers. Our findings suggest that ASD-associated risk factors contribute to the variability in symptom presentation in individuals with 16p11.2 CNVs. LAY SUMMARY: There are a wide range of autism spectrum disorder (ASD) symptoms and abilities observed for individuals with genetic changes of the 16p11.2 region. Here, we found perinatal complications contributed to more severe ASD symptoms (deletion carriers) and additional genetic mutations contributed to decreased cognitive abilities (deletion and duplication carriers). A potential protective factor was also observed for females with 16p11.2 variations. Autism Res 2020, 13: 1300-1310. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2332 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430

Genomic studies in fragile X premutation carriers / Reymundo LOZANO in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.27 Titre : Genomic studies in fragile X premutation carriers Type de document : texte imprimé Auteurs : Reymundo LOZANO, Auteur ; Randi J. HAGERMAN, Auteur ; Michael DUYZEND, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; Evan E. EICHLER, Auteur ; Flora TASSONE, Auteur Article en page(s) : p.27 Langues : Anglais (eng) Mots-clés : Asd  Autism  FMR1 gene  Neurodevelopmental disorders  Neurological disorders  Premutation  Second hit Index. décimale : PER Périodiques Résumé : BACKGROUND: The FMR1 premutation is defined as having 55 to 200 CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1). The clinical involvement has been well characterized for fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). The behavior/psychiatric and other neurological manifestations remain to be specified as well as the molecular mechanisms that will explain the phenotypic variability observed in individuals with the FMR1 premutation. METHODS: Here we describe a small pilot study of copy number variants (CNVs) in 56 participants with a premutation ranging from 55 to 192 repeats. The participants were divided into four different clinical groups for the analysis: those with behavioral problems but no autism spectrum disorder (ASD); those with ASD but without neurological problems; those with ASD and neurological problems including seizures; and those with neurological problems without ASD. RESULTS: We found 12 rare CNVs (eight duplications and four deletions) in 11 cases (19.6%) that were not found in approximately 8,000 controls. Three of them were at 10q26 and two at Xp22.3, with small areas of overlap. The CNVs were more commonly identified in individuals with neurological involvement and ASD. CONCLUSIONS: The frequencies were not statistically significant across the groups. There were no significant differences in the psychometric and behavior scores among all groups. Further studies are necessary to determine the frequency of second genetic hits in individuals with the FMR1 premutation; however, these preliminary results suggest that genomic studies can be useful in understanding the molecular etiology of clinical involvement in premutation carriers with ASD and neurological involvement. En ligne : http://dx.doi.org/10.1186/1866-1955-6-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] Genomic studies in fragile X premutation carriers [texte imprimé] / Reymundo LOZANO, Auteur ; Randi J. HAGERMAN, Auteur ; Michael DUYZEND, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; Evan E. EICHLER, Auteur ; Flora TASSONE, Auteur . - p.27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.27 Mots-clés : Asd  Autism  FMR1 gene  Neurodevelopmental disorders  Neurological disorders  Premutation  Second hit Index. décimale : PER Périodiques Résumé : BACKGROUND: The FMR1 premutation is defined as having 55 to 200 CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1). The clinical involvement has been well characterized for fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). The behavior/psychiatric and other neurological manifestations remain to be specified as well as the molecular mechanisms that will explain the phenotypic variability observed in individuals with the FMR1 premutation. METHODS: Here we describe a small pilot study of copy number variants (CNVs) in 56 participants with a premutation ranging from 55 to 192 repeats. The participants were divided into four different clinical groups for the analysis: those with behavioral problems but no autism spectrum disorder (ASD); those with ASD but without neurological problems; those with ASD and neurological problems including seizures; and those with neurological problems without ASD. RESULTS: We found 12 rare CNVs (eight duplications and four deletions) in 11 cases (19.6%) that were not found in approximately 8,000 controls. Three of them were at 10q26 and two at Xp22.3, with small areas of overlap. The CNVs were more commonly identified in individuals with neurological involvement and ASD. CONCLUSIONS: The frequencies were not statistically significant across the groups. There were no significant differences in the psychometric and behavior scores among all groups. Further studies are necessary to determine the frequency of second genetic hits in individuals with the FMR1 premutation; however, these preliminary results suggest that genomic studies can be useful in understanding the molecular etiology of clinical involvement in premutation carriers with ASD and neurological involvement. En ligne : http://dx.doi.org/10.1186/1866-1955-6-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346

---

1 (1 - 2 / 2) Par page : 25 50 100 200