Редактирование: FMR1 (раздел)

==Publications==

{{medline-entry
|title=Static and dynamic postural control deficits in aging fragile X mental retardation 1 ([[FMR1]]) gene premutation carriers.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30665341
|abstract=Individuals with premutation alleles of the fragile X mental retardation 1 ([[FMR1]]) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in [[FMR1]] premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS. We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS ), seven showed no MRI or neurological signs of FXTAS (FXTAS-), and four were inconclusive due to insufficient data. Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COP ) direction during static stance and reduced COP variability in the anterior-posterior (COP ) direction during dynamic AP sway. They also showed reductions in COP  complexity during each postural condition. FXTAS  individuals showed reduced COP  variability compared to FXTAS- carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities. Our findings indicate that aging [[FMR1]] premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS  and FXTAS- premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset.
|mesh-terms=* Aged
* Aging
* Ataxia
* Biomechanical Phenomena
* Cerebellum
* Female
* Fragile X Mental Retardation Protein
* Fragile X Syndrome
* Heterozygote
* Humans
* Magnetic Resonance Imaging
* Male
* Middle Aged
* Postural Balance
* Tremor
* Trinucleotide Repeat Expansion
|keywords=* Cerebellum
* FMR1gene premutation allele
* Fragile X mental retardation 1 (FMR1) gene
* Fragile X-associated tremor/ataxia syndrome (FXTAS)
* Postural control
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341725
}}
{{medline-entry
|title=Aging in Fragile X Premutation Carriers.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27334385
|abstract=It is now recognized that [[FMR1]] premutation carriers ([[PC]]) are at risk to develop a range of neurological, psychiatric, and immune-mediated disorders during adulthood. There are conflicting findings regarding the incidence of hypertension, hypothyroidism, diabetes, and cancer in these patients that warrant further study. A retrospective controlled study was performed in a convenience sample of 248 controls (130 men, 118 women) and 397 [[FMR1]] [[PC]] with and without fragile X-associated tremor ataxia syndrome (FXTAS) (176 men, 221 women); all participants were at least 45 years old (men: mean 62.4, SD 9.5; women: mean 62.8, SD 9.9; p = 0.63). Memory and cognitive assessments (Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III)) and molecular testing (CGG repeats and [[FMR1]]-mRNA levels) were performed. Additional data included body mass index (BMI), cholesterol levels, blood pressure, hemoglobin A1c (HbA1c) levels, and medical history. A higher percentage of [[PC]] subjects self-reported having a diagnosis of hypertension (50.0 vs. 35.0 %, p = 0.006) and thyroid problems (20.4 vs. 10.0 %, p = 0.012) than control subjects. When comparing controls versus [[PC]] with FXTAS, the association was higher for diabetes (p = 0.043); however, the effect was not significant after adjusting for demographic predictors. Blood pressure, blood glucose levels, HbA1c, and BMI values were not significantly different between the two groups. The [[PC]] with FXTAS group performed consistently lower in neuropsychological testing compared with the [[PC]] without FXTAS group, but the differences were very small for all but the WAIS full-scale IQ. Based on these findings, it appears that the risk for hypertension, thyroid problems, and diabetes may be more frequent in [[PC]] with FXTAS, which will require verification in future studies.
|mesh-terms=* Aging
* Ataxia
* Biomarkers
* Educational Status
* Female
* Fragile X Mental Retardation Protein
* Fragile X Syndrome
* Humans
* Least-Squares Analysis
* Male
* Middle Aged
* Neuropsychological Tests
* Prevalence
* Retrospective Studies
* Tremor
|keywords=* Ataxia
* Cognition
* FMR1
* FXTAS
* Fragile X syndrome
* Premutation
|full-text-url=https://sci-hub.do/10.1007/s12311-016-0805-x
}}
{{medline-entry
|title=A Majority of FXTAS Cases Present with Intranuclear Inclusions Within Purkinje Cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27108270
|abstract=Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder that affects carriers of a [[FMR1]] premutation. Symptoms include cerebellar ataxia, tremor, and cognitive deficits. The most characteristic pathology of FXTAS is the presence of eosinophilic ubiquitin-positive intranuclear inclusions in neurons and astrocytes throughout the nervous system and non-nervous tissues. Inclusions are present in neurons throughout the brain but are widely believed not to be present in the Purkinje cells ([[PC]]s) of the cerebellum. However, we analyzed 26 postmortem cases of FXTAS and demonstrated that 65 % of cases presented with inclusions within [[PC]]s of the cerebellum. We determined that the presence or absence of inclusions in [[PC]]s is correlated with age and that those cases with [[PC]] inclusions were overall 11 years older than those with no [[PC]] inclusions. Half of the cases with [[PC]]s with inclusions presented with twin nuclear inclusions. This novel finding demonstrating the presence of inclusions within [[PC]]s provides an insight into the understanding of the FXTAS motor symptoms and provides a novel target for the development of therapeutic strategies.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Ataxia
* Female
* Fragile X Syndrome
* Humans
* Intranuclear Inclusion Bodies
* Male
* Middle Aged
* Purkinje Cells
* Tremor
|keywords=* Cerebellum
* FRMP
* FXTAS
* Purkinje cells
* Ubiquitin
|full-text-url=https://sci-hub.do/10.1007/s12311-016-0776-y
}}
{{medline-entry
|title=Regional brain volumes changes in adult male [[FMR1]]-KO mouse on the FVB strain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26794591
|abstract=Fragile X Syndrome (FXS) is the most common heritable single gene cause of autism spectrum disorder (ASD). [[FMR1]]-KO mice mimic the etiology and phenotypic manifestations of FXS. Neuroanatomical changes in specific brain regions have been reported in clinical settings and in preclinical models. [[FMR1]]-KO mice have been generated in different strains including C57Bl/6 (B6) and FVB. Mice on different genetic backgrounds have stable yet distinct behavioral phenotypes that may lead to unique gene-strain interactions on brain structure. Previous magnetic resonance imaging (MRI) studies have examined [[FMR1]] knockout male mice on a B6 and found few differences compared to wild-type mice. Here, we examine brain volumes in [[FMR1]] knockout male mice on a FVB background using high resolution (multi-channel 7.0Tesla) MRI. We observe multiple differences in the neuroanatomy of male [[FMR1]]-/y mice on a FVB background. Significantly larger relative volume (% total brain volume) differences were found in major white matter structures throughout the brain. In addition, there were changes in areas associated with fronto-striatal circuitry and other regions. Functional and structural connectivity differences are often seen in human ASD, and therefore, this increased white matter seen in the [[FMR1]]-KO-FVB could be highlighting a structural over-connectivity, which could lead to some of the behavioral abnormalities seen with the [[FMR1]]-KO-FVB mice. Furthermore, these results highlight the importance of genetic strain contribution to brain structure. 
|mesh-terms=* Aging
* Animals
* Brain
* Disease Models, Animal
* Fragile X Mental Retardation Protein
* Fragile X Syndrome
* Mice, Knockout
* Motor Activity
* Phenotype
|keywords=* autism spectrum disorder
* genetic mouse model
* regional brain volumes
|full-text-url=https://sci-hub.do/10.1016/j.neuroscience.2016.01.021
}}
{{medline-entry
|title=[[FMR1]] premutation is an uncommon explanation for premature ovarian failure in Han Chinese.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25050920
|abstract=In premature ovarian failure (POF), cessation of menstruation occurs before the expected age of menopause. Approximately 1% of women are affected. [[FMR1]] premutation was reported to be responsible for up to 3.3%-6.7% of sporadic POF and 13% of familial cases in Caucasians, while the data was absent in Chinese population. Therefore, the impact of [[FMR1]] CGG repeat on ovarian reserve is needed to be investigated in large Chinese cohort. The number of [[FMR1]] CGG repeat was determined in 379 Han Chinese women with well-defined 46, XX non-syndromic sporadic POF and 402 controls. The age of menopause onset in respect to CGG repeats was further analyzed. The frequency of [[FMR1]] premutation in Han Chinese POF was only 0.5% (2/379), although it was higher than that in matched controls (0%, 0/402), it was much lower than that reported in Caucasian with POF (3.3%-6.7%). The prevalence of intermediate [[FMR1]] (41-54) was not increased significantly in sporadic POF than that in controls (2.9% vs. 1.7%, P = 0.343). However, POF patients more often carried a single additional CGG repeat in a single allele than did fertile women (allele-1: 29.7 vs. 28.8, P<0.001; allele-2: 32.6 vs. 31.5, P < 0.001). POF patients with both alleles of CGG repeats outside (below or above) the normal range (26-34) showed an earlier age of cessation of menses than those with two alleles within normal range (hom-high/high vs. norm: 20.4 ± 4.8 vs. 24.7 ± 6.4, p < 0.01; hom-low/high vs. norm: 18.7 ± 1.7 vs. 24.7 ± 6.4, p < 0.01). [[FMR1]] premutation seems to be an uncommon explanation for POF in Han Chinese. However, having both alleles with CGG repeats outside the normal range might still adversely affect ovarian aging.
|mesh-terms=* Adult
* Aging
* Alleles
* Asian Continental Ancestry Group
* China
* Female
* Fragile X Mental Retardation Protein
* Genotype
* Humans
* Menopause
* Ovary
* Primary Ovarian Insufficiency
* Trinucleotide Repeats

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106897
}}
{{medline-entry
|title=Age and CGG-repeat length are associated with neuromotor impairments in at-risk females with the [[FMR1]] premutation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24814676
|abstract=Recent studies report a higher risk of dementia and motor symptoms in females with the fragile X mental retardation 1 premutation (PM-carriers) than has hitherto been appreciated. Here, we use dual-task gait paradigms to identify potential markers of cognitive and motor decline in female PM-carriers. Spatiotemporal gait characteristics and variability of gait were assessed during single- and dual-task conditions in 28 female PM-carriers (mean age 41.32 ± 8.03 years) and 31 female controls with normal fragile X mental retardation 1 alleles (mean age 41.61 ± 8.30 years). Despite comparable gait characteristics at baseline, gait performance was significantly poorer for PM-carriers when performing concurrent working memory tasks (counting backwards by 3's or 7's) when compared with controls. Correlational analyses showed that low working memory capacity was significantly associated with dual-task interference for the gait domains of pace (speed, step length) and variability (step time, swing time) in PM-carriers. Multiple regression analyses further showed that the interaction between age and CGG repeat length was strongly predictive of gait variability during dual-task performance. These findings indicate for the first time that vulnerability in specific domains of gait control may act as sensitive surrogate markers of future decline in female PM-carriers.
|mesh-terms=* Adult
* Aging
* Female
* Fragile X Mental Retardation Protein
* Gait
* Genetic Association Studies
* Heterozygote
* Humans
* Memory, Short-Term
* Middle Aged
* Mutation
* Psychomotor Disorders
* Psychomotor Performance
* Regression Analysis
* Risk
* Trinucleotide Repeats
|keywords=* Alzheimer's disease
* Cerebellar motor networks
* Cognitive-motor interference
* Dual-task paradigm
* Fragile X mental retardation gene 1 (FMR1)
* Fragile X mental retardation protein (FMRP)
* Fragile X syndrome
* Fragile X tremor ataxia syndrome (FXTAS)
* Gait variability
* Working memory
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2014.03.018
}}
{{medline-entry
|title=Fragile X syndrome: an aging perspective.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23949830
|abstract=Cognitive and behavioral correlates of molecular variations related to the [[FMR1]] gene have been studied rather extensively, but research about the long-term outcome in individuals with fragile X spectrum disorders remains sparse. In this review, we present an overview of aging research and recent findings in regard to cellular and clinical manifestations of aging in fragile X syndrome, and the [[FMR1]] premutation.
|mesh-terms=* Aging
* Cerebellar Diseases
* Child Development Disorders, Pervasive
* Fragile X Mental Retardation Protein
* Fragile X Syndrome
* Humans
* Intellectual Disability
* Mosaicism
|keywords=* FMRP
* aging
* fragile X syndrome
* neurodegeneration
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959461
}}
{{medline-entry
|title=[[FMR1]]-dependent variability of ovarian aging patterns is already apparent in young oocyte donors.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23948096
|abstract=Hypothesizing that redundant functional ovarian reserve (FOR) at young ages may clinically obfuscate prematurely diminished FOR (PDFOR), we investigated in young oocyte donors genotypes and sub-genotypes of the [[FMR1]] gene, in prior studies associated with specific ovarian aging patterns, and determined whether they already at such young age were associated with variations in ovarian reserve (OR). We also investigated racial as well as [[FMR1]] associations with menarcheal age in these donors. In a cohort study we investigated 157 oocyte donor candidates and, based on the 95% CI of [[AMH]], divided them into normal age-specific ([[AMH]] greater or equal to 2.1 ng/mL; n = 121) and PDFOR ([[AMH]] < 2.1 ng/mL; n = 36). We then assessed associations between numbers of trinucleotide repeat (CGGn) on the [[FMR1]] gene and FOR (based on anti-Müllerian hormone, [[AMH]]). [[FMR1]] did not associate with [[AMH]] overall. Amongst 36 donors with PDFOR, 17 (42%) presented with at least one low (CGGn < 26 ) allele. Remaining donors with normal FOR presented with significantly more CGGn greater or equal to 26 (73.6% vs. 26.4%; P = 0.024) and higher [[AMH]] (P = 0.012). This finding was mostly the consequence of interaction between [[FMR1]] (CGGn < 26 vs. CGGn greater or equal to 26) and race (P = 0.013), with Asians most responsible (P = 0.009). Menarcheal age was in donors with normal FOR neither associated with race nor with [[FMR1]] status. In donors with PDFOR race was statistically associated with CGGn (P = 0.018), an association primarily based on significantly delayed age of menarche in African donors with CGGn < 26 in comparison to African donors with CGGn greater or equal to 26 (P = 0.019), and Caucasian (P = 0.017) and Asian donors (P = 0.025) with CGGn < 26. CGGn on [[FMR1]] already at young ages affects FOR, but is clinically apparent only in cases of PDFOR. Screening for low [[FMR1]] CGGn < 26 at young age, thus, appears predictive of later PDFOR.
|mesh-terms=* Adult
* African Continental Ancestry Group
* Aging
* Anti-Mullerian Hormone
* Asian Continental Ancestry Group
* Cohort Studies
* Ethnic Groups
* European Continental Ancestry Group
* Female
* Fragile X Mental Retardation Protein
* Genotype
* Humans
* Oocyte Donation
* Ovary
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751312
}}
{{medline-entry
|title=Cognitive-motor interference during postural control indicates at-risk cerebellar profiles in females with the [[FMR1]] premutation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23896050
|abstract=Recent investigations report a higher risk of motor symptoms in females with the [[FMR1]] premutation (PM-carriers) than has hitherto been appreciated. Here we examined basic sensorimotor and postural control under different sensory and attentional dual-task demands. Physiological performance and postural sway measures from the Physiological Profile Assessment (Lord et al., 2003 [39]) were conducted in 28 female PM-carriers (mean age: 41.32±8.03) and 31 female controls with normal [[FMR1]] alleles (mean age: 41.61±8.3). Multiple regression analyses were conducted to examine the moderating role of CGG-repeat length on the relation between age and postural sway under dual-task interference. In female PM-carriers, our results showed significantly poorer proprioceptive awareness, slower reaction time, and greater postural displacement when performing a concurrent verbal fluency task. Significantly, these findings showed age- and genetically-modulated changes in dual-task postural displacement in the medio-lateral direction in female PM-carriers. These findings highlight the sensitivity of postural control paradigms in identifying early cerebellar postural changes that may act as surrogate markers of future decline in female PM-carriers. 
|mesh-terms=* Adult
* Aging
* Cerebellum
* Cognition
* Cohort Studies
* DNA
* Female
* Fragile X Mental Retardation Protein
* Fragile X Syndrome
* Humans
* Middle Aged
* Movement
* Mutation
* Postural Balance
* Posture
* Proprioception
* Psychomotor Performance
* Trinucleotide Repeat Expansion
* Trinucleotide Repeats
* Verbal Behavior
* Young Adult
|keywords=* Cerebellar motor networks
* Cognitive-neuromotor interaction
* Fragile X Mental Retardation gene 1 (FMR1)
* Fragile X Mental Retardation protein (FMRP)
* Fragile X Tremor Ataxia Syndrome (FXTAS)
* Physiological Profile Assessment
* Postural control
|full-text-url=https://sci-hub.do/10.1016/j.bbr.2013.07.033
}}
{{medline-entry
|title=Language dysfluencies in females with the [[FMR1]] premutation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23523717
|abstract=Recent evidence suggests that there are age-related neurocognitive implications for fragile X premutation carriers, including deficits in executive function, and that such deficits are more common in male than female premutation carriers. The purpose of the current study is to examine one aspect of executive function, language dysfluencies, in a group of 193 women with the premutation, and to contrast them with a comparison group (mothers of children with autism spectrum disorders). Our results demonstrate a linguistic profile in the female premutation carriers characterized by dysfluencies associated with deficits in organization and planning, with a clear impact of age. The comparison group, matched on both age and education level, did not demonstrate the age effect. Our results suggest dysfluencies could be an early indicator of cognitive aging in some female premutation carriers, and could be used to target early intervention.
|mesh-terms=* Adult
* Age Factors
* Aged
* Aging
* Executive Function
* Female
* Fragile X Mental Retardation Protein
* Heterozygote
* Humans
* Language
* Middle Aged
* Mutation
* Speech Disorders

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625470
}}