Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome
The premutation expansion of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome has been linked to a range of clinical and subclinical features. Nearly half of men with FMR1 premutation develop a neurodegenerative disorder; Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)...
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MDPI AG
2022-11-01
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| author | Darren R. Hocking Danuta Z. Loesch Paige Stimpson Flora Tassone Anna Atkinson Elsdon Storey |
| author_facet | Darren R. Hocking Danuta Z. Loesch Paige Stimpson Flora Tassone Anna Atkinson Elsdon Storey |
| author_sort | Darren R. Hocking |
| collection | DOAJ |
| description | The premutation expansion of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome has been linked to a range of clinical and subclinical features. Nearly half of men with FMR1 premutation develop a neurodegenerative disorder; Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). In this syndrome, cognitive executive decline and psychiatric changes may co-occur with major motor features, and in this study, we explored the interrelationships between these three domains in a sample of adult males affected with FXTAS. A sample of 23 adult males aged between 48 and 80 years (mean = 62.3; SD = 8.8), carrying premutation expansions between 45 and 118 CGG repeats, and affected with FXTAS, were included in this study. We employed a battery of cognitive assessments, two standard motor rating scales, and two self-reported measures of psychiatric symptoms. When controlling for age and/or educational level, where appropriate, there were highly significant correlations between motor rating score for ICARS gait domain, and the scores representing global cognitive decline (ACE-III), processing speed (SDMT), immediate memory (Digit Span), and depression and anxiety scores derived from both SCL90 and DASS instruments. Remarkably, close relationships of UPDRS scores, representing the contribution of Parkinsonism to FXTAS phenotypes, were exclusive to psychiatric scores. Highly significant relationships between CGG repeat size and most scores for three phenotypic domains suggest a close tracking with genetic liability. These findings of relationships between a constellation of phenotypic domains in male PM carriers with FXTAS are reminiscent of other conditions associated with disruption to cerebro-cerebellar circuits. |
| first_indexed | 2024-03-09T18:27:11Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-09T18:27:11Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-3ad1e65e0882417dae4c7a8552cb61c82023-11-24T07:49:37ZengMDPI AGBrain Sciences2076-34252022-11-011211154910.3390/brainsci12111549Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia SyndromeDarren R. Hocking0Danuta Z. Loesch1Paige Stimpson2Flora Tassone3Anna Atkinson4Elsdon Storey5Developmental Neuromotor & Cognition Lab, School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3086, AustraliaSchool of Psychology and Public Health, La Trobe University, Melbourne, VIC 3086, AustraliaPsychology Department, Monash Health, Clayton, VIC 3068, AustraliaDepartment of Biochemistry and Molecular Medicine, M.I.N.D. Institute, School of Medicine, University of California Davis Medical Center, University of California, Davis, Davis, CA 95616, USASchool of Psychology and Public Health, La Trobe University, Melbourne, VIC 3086, AustraliaDepartment of Medicine (Neuroscience), Alfred Hospital Campus, Monash University, Melbourne, VIC 3068, AustraliaThe premutation expansion of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome has been linked to a range of clinical and subclinical features. Nearly half of men with FMR1 premutation develop a neurodegenerative disorder; Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). In this syndrome, cognitive executive decline and psychiatric changes may co-occur with major motor features, and in this study, we explored the interrelationships between these three domains in a sample of adult males affected with FXTAS. A sample of 23 adult males aged between 48 and 80 years (mean = 62.3; SD = 8.8), carrying premutation expansions between 45 and 118 CGG repeats, and affected with FXTAS, were included in this study. We employed a battery of cognitive assessments, two standard motor rating scales, and two self-reported measures of psychiatric symptoms. When controlling for age and/or educational level, where appropriate, there were highly significant correlations between motor rating score for ICARS gait domain, and the scores representing global cognitive decline (ACE-III), processing speed (SDMT), immediate memory (Digit Span), and depression and anxiety scores derived from both SCL90 and DASS instruments. Remarkably, close relationships of UPDRS scores, representing the contribution of Parkinsonism to FXTAS phenotypes, were exclusive to psychiatric scores. Highly significant relationships between CGG repeat size and most scores for three phenotypic domains suggest a close tracking with genetic liability. These findings of relationships between a constellation of phenotypic domains in male PM carriers with FXTAS are reminiscent of other conditions associated with disruption to cerebro-cerebellar circuits.https://www.mdpi.com/2076-3425/12/11/1549FMR1 premutationCGG repeatsFXTASmotor scorescognitive assessmentspsychiatric measures |
| spellingShingle | Darren R. Hocking Danuta Z. Loesch Paige Stimpson Flora Tassone Anna Atkinson Elsdon Storey Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome Brain Sciences FMR1 premutation CGG repeats FXTAS motor scores cognitive assessments psychiatric measures |
| title | Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome |
| title_full | Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome |
| title_fullStr | Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome |
| title_full_unstemmed | Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome |
| title_short | Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome |
| title_sort | relationships of motor changes with cognitive and neuropsychiatric features in fmr1 male carriers affected with fragile x associated tremor ataxia syndrome |
| topic | FMR1 premutation CGG repeats FXTAS motor scores cognitive assessments psychiatric measures |
| url | https://www.mdpi.com/2076-3425/12/11/1549 |
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