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The FMR1 premutation has been associated with difficulties in executive functioning, including verbal inhibition. However, little is known about the longitudinal profiles of verbal inhibition among FMR1 premutation carriers, particularly in women, and how individual factors such as aging and CGG repeat length may contribute to changes in verbal inhibition over time. The present study examined verbal inhibition performance (i.e., inhibition errors) on the Hayling Sentence Completion Task in a cohort of 92 women with the FMR1 premutation across two timepoints approximately three years apart. We examined the effects of age, CGG repeat length, and their interactions on verbal inhibition over time. We also evaluated whether response latency affected verbal inhibition errors. We found no significant change in verbal inhibition in the full cohort during the three-year study period. However, a subset of FMR1 premutation carriers, namely older participants with higher CGG repeats, evidenced greater declines in verbal inhibition over time. Longer response latencies did not compensate for verbal inhibition errors. The findings suggest that a subset of women with the FMR1 premutation may be at earlier, increased risk for changes in executive functioning, which if confirmed, should be considered as part of the clinical profile associated with the premutation.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Anciano , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Heterocigoto , Humanos , Masculino , Estudios Prospectivos , Expansión de Repetición de TrinucleótidoRESUMEN
Facial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 4,383 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci, highlighted a handful of candidate genes, and demonstrated enrichment for heritability in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.
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Belleza , Cara/anatomía & histología , Variación Genética , Adolescente , Alelos , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Estudios Longitudinales , Masculino , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Caracteres SexualesRESUMEN
BACKGROUND: Premutation-sized (55-200) CGG repeat expansions in the FMR1 gene cause fragile X-associated tremor/ataxia syndrome (FXTAS). Most studies of premutation carriers utilized reverse ascertainment to identify patients, leading to a selection bias for larger repeats. As shorter CGG premutation repeats are common in the population, understanding their impact on health outcomes has a potentially large public health footprint. OBJECTIVE: The study's objective was to compare an unselected group of premutation carriers (n = 35, 55-101 CGG repeats) with matched controls (n = 61, 29-39 CGG repeats) with respect to FXTAS-type signs using structured neurological assessments. METHODS: Three neurologists independently rated signs, using an adapted version of the FXTAS Rating Scale (Leehey MA, Berry-Kravis E, Goetz CG, et al. FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology. 2008). This was a double-blind study, as genetic status (premutation vs. control) was known neither by the participants nor by any of the neurologists. Analyses controlled potentially confounding comorbid conditions in the electronic health record (eg, osteoarthritis and stroke) and probed the association of age with signs. RESULTS: Although there was no overall difference between carriers and controls, among individuals without any potentially confounding comorbid diagnoses, there was a statistically significant age-associated elevation in FXTAS-type signs in premutation carriers compared to controls. CONCLUSIONS: Among those who do not have other comorbid diagnoses, women who have CGG repeats at the lower end of the premutation range may be at greater risk for ataxia and parkinsonism than their age peers, although their overall risk of developing such clinical features is low. This study should provide reassurance to those who share characteristics with the present cohort. © 2021 International Parkinson and Movement Disorder Society.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Heterocigoto , Ataxia/genética , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Humanos , Temblor/genética , Expansión de Repetición de TrinucleótidoRESUMEN
Individuals who carry a premutation (PM) allele on the FMR1 gene may experience executive limitations associated with their genetic status, including inhibition deficits. However, poor understanding of individualized risk factors has limited clinical management of this group, particularly in mothers who carry the PM allele who have children with fragile X syndrome (FXS). The present study examined CGG repeat length and age as factors that may account for variable expressivity of inhibition deficits. Participants were 134 carriers of the PM allele who were mothers of children with FXS. Inhibition skills were measured using both self-report and direct behavioral assessments. Increased vulnerability for inhibition deficits was observed at mid-range CGG lengths of approximately 80-100 repeats, with some evidence of a second zone of vulnerability occurring at approximately 130-140 CGG repeats. Risk associated with the genotype also became more pronounced with older age. This study identifies personalized risk factors that may be used to tailor the clinical management of executive deficits in carriers of the PM allele. Inhibition deficits may contribute to poor outcomes in carriers of the PM allele and their families, particularly in midlife and early old age, and clinical monitoring may be warranted.
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Función Ejecutiva , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Heterocigoto , Inhibición Psicológica , Expansión de Repetición de Trinucleótido , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Genotipo , Humanos , Persona de Mediana Edad , MadresRESUMEN
The FMR1 gene has been studied extensively with regard to expansions and premutations, but much less research has focused on potential effects of low CGG repeat length. Previous studies have demonstrated that BRCA1/2 positive women are more likely to have an FMR1 genotype with one low CGG allele, and that women with both FMR1 alleles in the low CGG repeat range are more likely to have had breast cancer compared to women with normal numbers of CGG repeats. However, there has been no research as to whether low CGG repeat length impacts cancer risks in men. Therefore, this study aimed to examine cancer incidence and related risk factors in men with low CGG repeat length in the FMR1 gene. We utilized subject data from the Marshfield Personalized Medicine Research Project to compare cancer-related diagnoses between 878 males with low CGG repeat length (< 24 repeats) and 368 male controls with CGG repeats in the normal range (24 to 40 repeats). We utilized ICD-9 codes to examine various cancer diagnoses, family histories of cancer, other non-malignant neoplasms, cancer surveillance, and genetic susceptibility. Men with low CGG repeats were identified to have significantly higher rates of family history of any cancer type (p = 0.011), family history of any BRCA-associated cancer (p = 0.002), and specifically, family history of prostate cancer (p = 0.007). The mean number of BRCA-associated cancer diagnoses (breast, prostate, pancreatic, and melanoma) per individual in the low CGG group was slightly higher than that of the control group, with this difference trending toward significance (p = 0.091). Additionally, men with low CGG repeats had significantly higher rates of connective/soft tissue neoplasms (p = 0.026). Additional research is needed to replicate the observations reported in this preliminary exploratory study, particularly including verification of ICD-9 codes and family history by a genetic counselor.
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Proteína BRCA1/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias/genética , Adulto , Alelos , Femenino , Genotipo , Humanos , Masculino , Registros Médicos , Factores de RiesgoRESUMEN
Individuals with autism spectrum disorder (ASD) experience higher rates of psychopathology than their typically developing peers or peers with other intellectual or developmental disabilities. Little is known about the developmental course of psychiatric symptoms such as internalizing and externalizing behaviors in this population. Individual characteristics and aspects of the family environment may explain variability in outcomes for adults with ASD. The present study extends our current understanding of psychopathology among individuals with ASD by examining group-based trajectories of internalizing and externalizing symptoms in adulthood. Overall, the results showed that symptoms became less severe over time. Distinct patterns of change in psychopathology were observed and associated with differential profiles of psychotropic medication use, comorbid mental health diagnoses, and residential placement. The likelihood of following each developmental trajectory was estimated based on characteristics of the adults with ASD (gender, adaptive behavior, and autistic symptoms) and maternal expressed emotion (criticism and warmth). Maternal criticism and warmth were identified as key risk and protective factors, respectively, with important implications for future research and intervention for individuals with ASD.
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Ansiedad/complicaciones , Trastorno del Espectro Autista/complicaciones , Depresión/complicaciones , Conducta Social , Adulto , Ansiedad/psicología , Trastorno del Espectro Autista/psicología , Mecanismos de Defensa , Depresión/psicología , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
INTRODUCTION: In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology. METHODS: PET imaging with carbon 11-labeled Pittsburgh compound B examined the pattern of amyloid-ß deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellar gray matter as the reference region. RESULTS: Multiple linear regression revealed slight but highly significant (corrected P < .05) positive correlations between SUVR and age. The striatum showed the strongest correlation, followed by precuneus, parietal cortex, anterior cingulate, frontal cortex, and temporal cortex. CONCLUSION: There is an age-related amyloid-ß deposition in the DS population, but as a pattern of elevated cortical retention becomes apparent, the correlation of SUVR with age ceases to be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.
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Envejecimiento/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Síndrome de Down/diagnóstico por imagen , Síndrome de Down/metabolismo , Adulto , Compuestos de Anilina , Apolipoproteínas E/genética , Radioisótopos de Carbono , Estudios de Cohortes , Síndrome de Down/genética , Femenino , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , TiazolesRESUMEN
Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-ß deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-ß deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P < 0.0001) between age and neocortical Pittsburgh compound B retention. This robust association makes it difficult to discriminate normative age-related decline in cognitive functioning from any potential effects of amyloid-ß deposition. When controlling for chronological age in addition to mental age, there were no significant differences between the adults with Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-ß deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-ß deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-ß deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.
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Péptidos beta-Amiloides/fisiología , Encéfalo/metabolismo , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/psicología , Síndrome de Down/fisiopatología , Síndrome de Down/psicología , Adulto , Compuestos de Anilina/administración & dosificación , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Trastornos del Conocimiento/metabolismo , Síndrome de Down/metabolismo , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neocórtex/metabolismo , Neocórtex/fisiopatología , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones/métodos , Tiazoles/administración & dosificaciónRESUMEN
The pathophysiological consequences of caregiving have not been fully elucidated. We evaluated how caregiving, stress, and caregiver strain were associated with shorter relative telomere length (RTL), a marker of cellular aging. Caregivers (n = 240) and some noncaregivers (n = 98) in the 2008-2010 Survey of the Health of Wisconsin, comprising a representative sample of Wisconsin adults aged 21-74 years, reported their sociodemographic, health, and psychological characteristics. RTL was assayed from blood or saliva samples. Median T and S values were used to determine the telomere-to-single copy gene ratio (T/S) for each sample, and log(T/S) was used as the dependent variable in analyses. Multivariable generalized additive models showed that RTL did not differ between caregivers and noncaregivers (difference in log(T/S) = -0.03; P > 0.05), but moderate-to-high levels of stress versus low stress were associated with longer RTL (difference = 0.15; P = 0.04). Among caregivers, more hours per week of care, caring for a young person, and greater strain were associated with shorter RTL (P < 0.05). Caregivers with discordant levels of stress and strain (i.e., low perceived stress/high strain) compared with low stress/low strain had the shortest RTL (difference = -0.24; P = 0.02, Pinteraction = 0.13), corresponding to approximately 10-15 additional years of aging. Caregivers with these characteristics may be at increased risk for accelerated aging. Future work is necessary to better elucidate these relationships and develop interventions to improve the long-term health and well-being of caregivers.
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Cuidadores/psicología , Estrés Psicológico/fisiopatología , Acortamiento del Telómero , Adulto , Anciano , Cuidadores/estadística & datos numéricos , Estudios de Casos y Controles , Senescencia Celular , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Análisis Multivariante , Factores de Riesgo , WisconsinRESUMEN
In a sample of post-menopausal premutation carrier mothers of children with the full mutation of fragile X syndrome (n = 88), this study examined the co-occurrence of the reproductive and psychiatric phenotypes associated with FMR1 premutations. Mean age at menopause was 43.1 years, and 35.2% of premutation carriers reported cessation of menses prior to age 40 (premature ovarian failure), but only 18% of carriers had been medically diagnosed by a physician as having Fragile X-associated Primary Ovarian Insufficiency. There was a significant curvilinear association between CGG repeat length and age at menopause, with women who had mid-range repeats having the earliest menopause, similar to the pattern that has been found for the psychiatric phenotype of the FMR1 premutation.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Menopausia/genética , Mutación/genética , Insuficiencia Ovárica Primaria/genética , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Persona de Mediana Edad , FenotipoRESUMEN
Autistic adults experience challenges in maintaining employment; however, little is known about patterns of competitive employment through late midlife. This longitudinal study examined the change in hours of competitive employment for a cohort of autistic adults over a 22-year period. The study's aims were to provide a fine-grained analysis of competitive employment patterns, to determine whether there was age-related change, and to test whether trajectories differed between those with and without intellectual disability (ID). Using an accelerated longitudinal design, trajectories of hours of competitive employment were estimated from young adulthood through late midlife in a community-based cohort (n = 341; 1327 observations). Results indicated a significant curvilinear trajectory of age-related change in hours of competitive employment, with differences between those with and without ID. For those without ID, the number of competitive employment hours increased from young adulthood until early midlife, then leveled off and decreased into late midlife. For those with ID, engagement in competitive employment was low throughout. Although competitive employment is just one option for vocational engagement, it is a goal often articulated by autistic adults who seek entry into the general workforce. The present research reveals their degree of engagement in the competitive workforce across the decades of adulthood.
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Autistic individuals and their families are at risk for poor outcomes in employment and mental health and may be vulnerable to long-term effects of broader societal conditions. The aim of the current longitudinal study was to understand the impact of the Great Recession of 2007-2009 on autistic individuals and their mothers (N = 392). Hierarchical linear modeling (HLM) results indicated that problem behavior of autistic adults increased in the years following the recession. The rate at which autistic individuals moved away and lived separately from their mothers also slowed during the recession. Mothers experienced significantly higher levels of depressive symptoms postrecession, compared to prerecession. In many other respects, the autistic individuals and their mothers did not experience negative outcomes, suggesting resilience and a strong safety net. These included the physical health and vocational/employment status of the autistic adults and their mothers. Results point to specific areas of vulnerability of autistic individuals and their mothers during the economic downturn, as well as a broad pattern of resilience in these families.
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Trastorno Autístico , Adulto , Femenino , Humanos , Trastorno Autístico/epidemiología , Trastorno Autístico/psicología , Estudios Longitudinales , Madres/psicología , Salud Mental , EmpleoRESUMEN
We have estimated the prevalence of FMR1 premutation and gray zone CGG repeat expansions in a population-based sample of 19,996 male and female adults in Wisconsin and compared the observed sex ratios of the prevalence of FMR1 CGG premutation and gray zone expansions to theoretical sex ratios. The female premutation prevalence was 1 in 148 and comparable to past research, but the male premutation prevalence of 1 in 290 is somewhat higher than most previous estimates. The female:male premutation prevalence ratio is in line with the theoretically predicted sex ratio. The prevalence of CGG repeats in the gray zone (45-54 repeats) was 1 in 33 females and 1 in 62 males. The prevalence of the "expanded" gray zone (defined here as 41-54 CGG repeats) was 1 in 14 females and 1 in 22 males, leading to a female:male ratio of 1.62 (95% confidence interval 1.39-1.90). This female:male ratio was significantly lower than the expected ratio of 2.0. We examined results from three previously published FMR1 prevalence studies and found similar female:male ratios for CGG repeats in this "expanded" gray zone range (pooled female:male ratio across all four studies 1.66, 95% confidence interval 1.51-1.82). Further research is needed to understand the apparent excess prevalence of males with CGG repeats in this range.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Razón de Masculinidad , Repeticiones de Trinucleótidos , Adulto , Femenino , Síndrome del Cromosoma X Frágil/epidemiología , Síndrome del Cromosoma X Frágil/genética , Frecuencia de los Genes , Humanos , Masculino , Mutación , Prevalencia , Wisconsin/epidemiologíaRESUMEN
Developmental disabilities (DD) research has depended on volunteer and clinical samples, with limited racial/ethnic diversity. This study focused on improving diversity and retention in DD research. The sample included 225 parents with a child with DD and 4,002 parents without children with DD from diverse racial/ethnic groups, drawn from Midlife in the United States, a national longitudinal study. Unexpectedly, parents of children with DD from diverse racial/ethnic groups were more likely to participate longitudinally than other groups. Relative participant payment was a factor that enhanced their likelihood of retention. This research illustrates how large national studies can be leveraged to increase representativeness and ongoing participation of diverse racial/ethnic groups, especially in combination with other factors, such as parenting a child with DD.
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Discapacidades del Desarrollo , Padres , Niño , Humanos , Estados Unidos , Estudios Longitudinales , Responsabilidad Parental , Grupo SocialRESUMEN
The present study examined the associations between networks of social relationships and psychological well-being among mothers of adolescents and adults with autism (n = 352) over a 12-year period of time. A structural equation modeling approach was used to delineate the relative impacts of network size and relationship diversity on maternal mental health, and to assess whether such effects are bidirectional. Mothers with more diverse relationships experienced reductions in depression and anxiety symptoms over time, and the psychological benefits of diversity remained after adjusting for network size. Results also suggest bidirectional links between network size, diversity, and maternal mental health. Research and clinical implications are discussed.
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Trastorno del Espectro Autista , Trastorno Autístico , Adulto , Femenino , Adolescente , Humanos , Madres/psicología , Salud Mental , Depresión/psicología , Red Social , Trastorno del Espectro Autista/psicologíaRESUMEN
Sleep plays an integral role in supporting well-being, and sleep difficulties are common in mothers of individuals with developmental disabilities, including fragile X syndrome (FXS). This study assessed whether the effects of sleep quality on physical health and depression are exacerbated by genetic risk factors (CGG repeats) in FMR1 premutation carrier mothers of individuals with FXS. Poor sleep quality predicted a greater number of physical health conditions for mothers with CGG repeats in the mid-premutation range (90-110 repeats), but not for those in the lower (< 90 repeats) or higher (> 110 repeats) ends of the range. A significant association between poor sleep quality and maternal depressive symptoms was also observed, but there was no evidence that this effect varied by level of genetic vulnerability. This research extends our understanding of individual differences in the effects of sleep quality among mothers of individuals with FXS.
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Síndrome del Cromosoma X Frágil , Femenino , Humanos , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Calidad del Sueño , Madres , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , SueñoRESUMEN
Higher education has been shown to have neuroprotective effects, reducing the risk of Alzheimer's and Parkinson's diseases, slowing the rate of age-related cognitive decline, and is associated with lower rates of early mortality. In the present study, the association between higher education, fragile X messenger ribonucleoprotein 1 (FMR1) cytosine-guanine-guanine (CGG) repeat number, and mortality before life expectancy was investigated in a population cohort of women born in 1939. The findings revealed a significant interaction between years of higher education and CGG repeat number. Counter to the study's hypothesis, the effects of higher education became more pronounced as the number of CGG repeats increased. There was no effect of years of higher education on early mortality for women who had 25 repeats, while each year of higher education decreased the hazard of early mortality by 8% for women who had 30 repeats. For women with 41 repeats, the hazard was decreased by 14% for each additional year of higher education. The interaction remained significant after controlling for IQ and family socioeconomic status (SES) measured during high school, as well as factors measured during adulthood (family, psychosocial, health, and financial factors). The results are interpreted in the context of differential sensitivity to the environment, a conceptualization that posits that some people are more reactive to both negative and positive environmental conditions. Expansions in CGG repeats have been shown in previous FMR1 research to manifest such a differential sensitivity pattern.
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Disfunción Cognitiva , Fármacos Neuroprotectores , Enfermedad de Parkinson , Humanos , Femenino , Anciano de 80 o más Años , Adulto , Citosina , Guanina , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genéticaRESUMEN
The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Humanos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Mutación/genética , ARN Mensajero/metabolismo , Expansión de Repetición de Trinucleótido/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/terapiaRESUMEN
Although an increasing number of individuals with autism spectrum disorders are entering adulthood, currently there are few evidence-based programs for individuals later in the life course. In this paper we present an overview of recent research on outcomes for adolescents and adults with ASD and highlight the role of the family for individuals with ASD during the transition to adulthood. We also discuss multi-family group psychoeducation as a promising model for use with individuals with ASD who are transitioning to adulthood.
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Trastornos Generalizados del Desarrollo Infantil/terapia , Familia/psicología , Padres/educación , Adolescente , Adulto , Niño , Curriculum , Educación en Salud/métodos , Necesidades y Demandas de Servicios de Salud , Humanos , Modelos Psicológicos , Padres/psicología , Proyectos PilotoRESUMEN
BACKGROUND: Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length. METHODS: Forty-five women with the FMR1 premutation aged 35-64 years at study entry participated in 1-5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing. RESULTS: Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change. CONCLUSIONS: Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation.