Browsing by Author "Tassone, Flora (7006128050)"

Background: The majority of individuals with fragile X syndrome (FXS) have intellectual disability, behavioral problems, autism, and language deficits. IQ typically declines with age in boys with the full mutation. The results of preclinical studies demonstrated that metformin, a biguanide used to treat type 2 diabetes, rescues multiple phenotypes of FXS in both Drosophila and mouse models. Preliminary studies of patients with FXS demonstrated improvements in behavior. Methods: Here, we present two cases of individuals who have been treated with metformin clinically for one year. Results: Both patients demonstrated significant cognitive and behavioral improvements. They also improved eating habits and normalization of their weight percentiles. Conclusion: Metformin may be a candidate drug for treatment of several types of symptoms in individuals with FXS. © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Background: The majority of individuals with fragile X syndrome (FXS) have intellectual disability, behavioral problems, autism, and language deficits. IQ typically declines with age in boys with the full mutation. The results of preclinical studies demonstrated that metformin, a biguanide used to treat type 2 diabetes, rescues multiple phenotypes of FXS in both Drosophila and mouse models. Preliminary studies of patients with FXS demonstrated improvements in behavior. Methods: Here, we present two cases of individuals who have been treated with metformin clinically for one year. Results: Both patients demonstrated significant cognitive and behavioral improvements. They also improved eating habits and normalization of their weight percentiles. Conclusion: Metformin may be a candidate drug for treatment of several types of symptoms in individuals with FXS. © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Background: The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. Methods: This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.9%) or identified through the cascade testing (non-probands, 54.1%) of an affected sibling with fragile X syndrome. Information on the presence of autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, long-term psychiatric medication intake, and cognitive function, based on standardized assessments, was obtained. Molecular data, including CGG repeat number and FMR1 mRNA levels, were also available for a subset of participants. Analysis included descriptive statistics and a test of comparison to describe the clinical profile of PM individuals pertinent to FXAND. Results: Participants included 61 individuals (52 males and 9 females) aged 7.8 to 20.0 years (mean 12.6 ± 3.4) with a mean full-scale IQ of 90.9 ± 22.7. The majority (N = 52; 85.2%) had at least one mental health disorder, with anxiety being the most common (82.0% of subjects), followed by ADHD (66.5%), and ASD (32.8%). Twenty-seven (87.1%) of non-probands also had at least one mental health condition, with probands having lower cognitive and adaptive skills than non-probands. ASD was present in 20 participants (17/52 males and 3/9 females; 15 probands) with significantly lower FSIQ in those with ASD (mean 73.5 vs. 98.0, p < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, p = 0.002). Conclusions: Our findings indicate a high rate of FXAND diagnoses within a cohort of young PM individuals, including those identified via cascade testing, although this was not a population sample. An awareness of the entity of FXAND and the early recognition of the symptoms of associated conditions may facilitate timely and appropriate care for PM individuals. © 2022 by the authors.

Background: The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. Methods: This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.9%) or identified through the cascade testing (non-probands, 54.1%) of an affected sibling with fragile X syndrome. Information on the presence of autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, long-term psychiatric medication intake, and cognitive function, based on standardized assessments, was obtained. Molecular data, including CGG repeat number and FMR1 mRNA levels, were also available for a subset of participants. Analysis included descriptive statistics and a test of comparison to describe the clinical profile of PM individuals pertinent to FXAND. Results: Participants included 61 individuals (52 males and 9 females) aged 7.8 to 20.0 years (mean 12.6 ± 3.4) with a mean full-scale IQ of 90.9 ± 22.7. The majority (N = 52; 85.2%) had at least one mental health disorder, with anxiety being the most common (82.0% of subjects), followed by ADHD (66.5%), and ASD (32.8%). Twenty-seven (87.1%) of non-probands also had at least one mental health condition, with probands having lower cognitive and adaptive skills than non-probands. ASD was present in 20 participants (17/52 males and 3/9 females; 15 probands) with significantly lower FSIQ in those with ASD (mean 73.5 vs. 98.0, p < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, p = 0.002). Conclusions: Our findings indicate a high rate of FXAND diagnoses within a cohort of young PM individuals, including those identified via cascade testing, although this was not a population sample. An awareness of the entity of FXAND and the early recognition of the symptoms of associated conditions may facilitate timely and appropriate care for PM individuals. © 2022 by the authors.

Background: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show a significant impact of AFQ056 on language development in children with fragile X syndrome aged 3–6 years. Objectives: The current analyses from biospecimens collected in the FXLEARN study aimed to determine whether AFQ056 affects the level of potential biomarkers associated with Akt/mTOR and matrix metalloproteinase 9 signaling in young individuals with fragile X syndrome. Previous research has indicated that these biomarkers play crucial roles in the pathophysiology of fragile X syndrome. Design: A double-blind placebo-controlled parallel-group flexible-dose forced titration design. Methods: Blood samples for biomarkers were collected during the FXLEARN at baseline and subsequent visits (1- and 8-month visits). Biomarker analyses included fragile X messenger ribonucleoprotein-1 genotyping by Southern blot and PCR approaches, fragile X messenger ribonucleoprotein-1 mRNA levels determined by PCR, matrix metalloproteinase 9 levels’ detection using a magnetic bead panel, and targets of the Akt/mTOR signaling pathway with their phosphorylation levels detected. Results: This research revealed that administering AFQ056 does not affect the expression levels of the investigated blood biomarkers in young children with fragile X syndrome. Conclusion: Our findings of the lack of association between clinical improvement and biomarkers’ levels in the treatment group are in line with the lack of benefit observed in the FXLEARN study. These findings indicate that AFQ056 does not provide benefits as assessed by primary or secondary endpoints. Registration: ClincalTrials.gov NCT02920892. © The Author(s) 2024.

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that usually begins in the early 60s and affects carriers of premutation expansion (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Additional disorders can co-occur with FXTAS including Alzheimer’s disease (AD). Here we discuss a case report of a male with 67 CGG repeats in FMR1 who had mild late-onset FXTAS symptoms followed by neurocognitive disorder symptoms consistent with AD. The patient has developed tremor and ataxia that are the two characteristic symptoms of FXTAS. In addition, he shows rapid cognitive decline, brain atrophy most substantial in the medial temporal lobe, and decreased metabolism in the brain regions that are the characteristic findings of AD. The purpose of this study is to describe a patient profile with both diseases and review the details of an overlap between these two diseases. © 2020 Aydin et al.