Fragile X-Associated Disorders in Serbia: Baseline Quantitative and Qualitative Survey of Knowledge, Attitudes and Practices Among Medical Professionals

We conducted a knowledge, attitude, and practice (KAP) survey of fragile X-associated disorders (FXD) in Serbia in order to obtain baseline quantitative and qualitative KAP data on fragile X mental retardation 1 gene (FMR1) pre- and full mutations (PM, FM). The survey's 16-item questionnaire included a knowledge component (12/16), such as self-assessment knowledge (SAK) and factual knowledge (FK, 2/5 questions for PM, FXTAS and FXPOI). Education-directed attitudes in the FXD field and FMR1 DNA testing practices had 4/16 items, including brief case vignettes of FXTAS and FXPOI, respectively. The study's cohort consisted of primary care physicians (referred to as “physicians” in the rest of the text) throughout Serbia (n = 284, aged 26–64 years, 176/284, 62.2% in Belgrade, Serbia) and senior medical students (n = 245, aged 23–30 years; 33.5% males) at the Belgrade School of Medicine. Strikingly, half of the survey respondents indicated “not having any” knowledge for the fragile X gene premutation and FXD. Physicians were more likely to indicate “not having any” knowledge than students (41.2% of physicians vs. 13.1% of students, P < 0.05). Roughly half of the students had “minimal knowledge” (53.5 vs. 30.5% of physicians, P < 0.05). Low FK was common in the cohort, as few physicians had “all correct answers” (7.5 vs. 3.7% of students, P < 0.05; 16.5 vs. 9.5% of students for the 2/5 premutation-related questions). Statistical analyses identified physicians' practice setting and length of clinical experience as predictors of the lack of FK on questions related to FXD. Physicians were more likely than students to indicate “strongly agreed” to expand their knowledge of the gene premutation and FXD (90.9 vs. 66.7% of students, P < 0.01). However, students more frequently indicated that they are willing to recommend DNA testing in their future practices than physicians (93.5 vs. 64.8% of physicians, P < 0.001). In conclusion, there is a major gap in knowledge regarding fragile X gene PM and FXD among the study's participants in Serbia. The study's informative-educational survey serves as an initial step in the process of enhancing the KAP of medical professionals with regards to the fragile X gene premutation and FXD

Cerebral expression of metabotropic glutamate receptor subtype 5 in idiopathic autism spectrum disorder and fragile X syndrome: A pilot study

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGlu

Reduced expression of cerebral metabotropic glutamate receptor subtype 5 in men with fragile X syndrome

Glutamatergic receptor expression is mostly unknown in adults with fragile X syndrome (FXS). Favorable behavioral effects of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGlu

Fragile X Mental Retardation Protein and cerebral expression of metabotropic glutamate receptor subtype 5 in men with fragile X syndrome: A pilot study

Multiple lines of evidence suggest that a deficiency of Fragile X Mental Retardation Protein (FMRP) mediates dysfunction of the metabotropic glutamate receptor subtype 5 (mGlu

Fragile X Syndrome: Recent Research Updates toward Capturing Treatments’ Improvement in Clinical Trials

This Brain Sciences 2020 Special Issue of nine manuscripts contribute novel data on treatment updates in fragile X syndrome (FXS) [...

FMR1 gene mutations cause neurodevelopmental-degenerative disorders: Importance of fragile X testing in Serbia

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Fragile X syndrome: Lessons learned from the most translated neurodevelopmental disorder in clinical trials

Fragile X syndrome (FXS) is the leading genetic cause of autism spectrum disorder (ASD) and inherited intellectual disability (ID) worldwide. Preclinical successes in understanding the biology of FXS have led to numerous translational attempts in human clinical trials of therapeutics that target the excitatory/inhibitory neural signaling imbalances thought to underlie FXS. Despite the preclinical success story, the negative results of the human clinical trials have been deemed to be at least in part disappointing by the field. In this commentary, we contend that such negative studies results in clinical trials may actually propel the FXS field forward by serving as important lessons for designing and implementing improved future clinical trials such that can objectively assess the full range of responses to new therapeutics

Genomic studies in fragile X premutation carriers.

BackgroundThe FMR1 premutation is defined as having 55 to 200 CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1). The clinical involvement has been well characterized for fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). The behavior/psychiatric and other neurological manifestations remain to be specified as well as the molecular mechanisms that will explain the phenotypic variability observed in individuals with the FMR1 premutation.MethodsHere we describe a small pilot study of copy number variants (CNVs) in 56 participants with a premutation ranging from 55 to 192 repeats. The participants were divided into four different clinical groups for the analysis: those with behavioral problems but no autism spectrum disorder (ASD); those with ASD but without neurological problems; those with ASD and neurological problems including seizures; and those with neurological problems without ASD.ResultsWe found 12 rare CNVs (eight duplications and four deletions) in 11 cases (19.6%) that were not found in approximately 8,000 controls. Three of them were at 10q26 and two at Xp22.3, with small areas of overlap. The CNVs were more commonly identified in individuals with neurological involvement and ASD.ConclusionsThe frequencies were not statistically significant across the groups. There were no significant differences in the psychometric and behavior scores among all groups. Further studies are necessary to determine the frequency of second genetic hits in individuals with the FMR1 premutation; however, these preliminary results suggest that genomic studies can be useful in understanding the molecular etiology of clinical involvement in premutation carriers with ASD and neurological involvement