Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

Zafarullah, Marwa; Tassone, Flora

doi:10.1007/978-1-4939-9080-1_15

Cited by 7 publications

(6 citation statements)

References 60 publications

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“…FXTAS stage scoring was based on the clinical descriptions as previously described 21 . As explained by, 22 there are three categories used in the diagnosis of FXTAS termed as “definite,” “probable,” and “possible.” “Definite” indicates the presence of one major radiological sign plus one major clinical symptom. “Probable” shows the presence of either one major radiology sign plus one minor clinical symptom or two major clinical symptoms.…”

Section: Methodsmentioning

confidence: 99%

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Metabolic profiling reveals dysregulated lipid metabolism and potential biomarkers associated with the development and progression of Fragile X‐Associated Tremor/Ataxia Syndrome (FXTAS)

et al. 2020

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Section: Methodsmentioning

confidence: 99%

“…FXTAS stage scoring was based on the clinical descriptions as previously described. 21 As explained by, 22 there are three categories used in the diagnosis of FXTAS termed as "definite," "probable," and "possible." "Definite" indicates the presence of one major radiological sign plus one major clinical symptom.…”

Section: Study Participantsmentioning

confidence: 99%

Metabolic profiling reveals dysregulated lipid metabolism and potential biomarkers associated with the development and progression of Fragile X‐Associated Tremor/Ataxia Syndrome (FXTAS)

et al. 2020

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“…FXTAS stage scoring was based on the clinical descriptions as previously described (26). Three categories were used in the diagnosis of FXTAS as explained in Zafarullah and Tassone (27) and termed as "definite, " "probable" and "possible." Three agematched groups were included in this study: CON, NCON, and HC.…”

Section: Study Participantsmentioning

confidence: 99%

Metabolomic Biomarkers Are Associated With Area of the Pons in Fragile X Premutation Carriers at Risk for Developing FXTAS

et al. 2021

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder that affects movement and cognition in male and female carriers of a premutation allele (55–200 CGG repeats; PM) in the fragile X mental retardation (FMR1) gene. It is currently unknown how the observed brain changes are associated with metabolic signatures in individuals who develop the disorder over time. The primary objective of this study was to investigate the correlation between longitudinal changes in the brain (area of the pons, midbrain, and MCP width) and the changes in the expression level of metabolic biomarkers of early diagnosis and progression of FXTAS in PM who, as part of an ongoing longitudinal study, emerged into two distinct categories. These included those who developed symptoms of FXTAS (converters, CON) at subsequent visits and those who did not meet the criteria of diagnosis (non-converters, NCON) and were compared to age-matched healthy controls (HC). We assessed CGG repeat allele size by Southern Blot and PCR analysis. Magnetic Resonance Imaging (MRIs) acquisition was obtained on a 3T Siemens Trio scanner and metabolomic profile was obtained by ultra-performance liquid chromatography, accurate mass spectrometer, and an Orbitrap mass analyzer. Our findings indicate that differential metabolite levels are linked with the area of the pons between healthy control and premutation groups. More specifically, we observed a significant association of ceramides and mannonate metabolites with a decreased area of the pons, both at visit 1 (V1) and visit 2 (V2) only in the CON as compared to the NCON group suggesting their potential role in the development of the disorder. In addition, we found a significant correlation of these metabolic signatures with the FXTAS stage at V2 indicating their contribution to the progression and pathogenesis of FXTAS. Interestingly, these metabolites, as part of lipid and sphingolipid lipids pathways, provide evidence of the role that their dysregulation plays in the development of FXTAS and inform us as potential targets for personalized therapeutic development.

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“…Women of reproductive age diagnosed with FXPOI may have symptoms of low minerals bone density, osteoporosis, bone fractures [ 10 , 11 ] and fibromyalgia [ 12 ] PM carrier women may experience obstetric and perinatal difficulties like late pregnancy bleeding [ 13 ] and vestibular issues such as dizziness, spinning and not able to balance body [ 14 ]. PM carrier women may suffer from hypertension, central pain sensitivity syndrome, sleep problems, restless legs syndrome, migraine and gait issues [ 15 ]. Depression, anxiety and attention problems were more commonly observed psychiatric features in PM carriers [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Fragile X premutation carrier screening in Pakistani preconception women in primary care consultation

et al. 2022

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Purpose Women of reproductive age who carry fragile X premutation (PM) alleles have 56 to 200 CGG repeats in the 5′-untranslated region of FMR1 gene are at increased risk for producing children with intellectual disabilities (ID) or autism spectrum disorders (ASD) due to expansion of PM alleles to full mutation alleles (> 200 repeats) during maternal transmission. Methods In present study fragile X PM carrier screening was performed in total 808 women who were consulting primary health care centers for preconception care in Khyber Pakhtunkhwa region of Pakistan between April, 2018 and December, 2020. Polymerase chain reaction (PCR) was performed for detection of PM carrier women and the CGG repeats number was confirmed by Southern blotting and capillary electrophoresis. Results The prevalence rate for PM carriers among preconception women was found to be 0.7% that was contributed by 0.5% women in risk group (RG1) with family history of ID and 0.2% in risk group 2 (RG2) with family history of ASD. PM carrier women had at least one affected child or sibling. In addition, the preconception women with FMR1 PM alleles were found to be at increased risk for primary ovary insufficiency (RG1: P = 0.0265, RG2: P = 0.0389), postpartum depression (RG1: P = 0.0240, RG2: P = 0.0501) and neuropsychiatric disorders (RG1: P = 0.0389, RG2: P = 0.0432). Conclusions Current study provides first evidence of fragile X PM carrier screening in Pakistani preconception women in primary care consultation. Findings of current study may help to improve preconception care and to reduce burden of fragile X associated disorders in our population.

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Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

Cited by 7 publications

References 60 publications

Metabolic profiling reveals dysregulated lipid metabolism and potential biomarkers associated with the development and progression of Fragile X‐Associated Tremor/Ataxia Syndrome (FXTAS)

Metabolic profiling reveals dysregulated lipid metabolism and potential biomarkers associated with the development and progression of Fragile X‐Associated Tremor/Ataxia Syndrome (FXTAS)

Metabolomic Biomarkers Are Associated With Area of the Pons in Fragile X Premutation Carriers at Risk for Developing FXTAS

Fragile X premutation carrier screening in Pakistani preconception women in primary care consultation

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