Publications by authors named "Dicaire M"

Objective: Late-onset cerebellar ataxia (LOCA) is a slowly progressive cerebellar disorder with symptom onset ≥30years of age. Intronic tandem repeat expansions (TREs) in RFC1 and FGF14 have recently emerged as common causes of LOCA. The relative contribution of classic vs.

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Objectives: To report a novel imaging finding of bilateral dentate nuclei hyperintensities in a case of childhood-onset GAA--related ataxia (spinocerebellar ataxia 27B, SCA27B) and response to 4-aminopyridine (4-AP).

Methods: A 53-year-old woman with unsolved progressive cerebellar ataxia of childhood onset underwent clinical and imaging assessment and extensive genetic investigation.

Results: After excluding Friedreich ataxia, most common spinocerebellar ataxia-related expansions, and pathogenic variants in ataxia-related genes through exome sequencing, targeted long-range PCR and repeat-primed PCR analysis revealed a heterozygous pathogenic (GAA) expansion in Brain MRI showed bilateral dentate nuclei hyperintensities and peridentate white matter degeneration, a feature never reported before in SCA27B.

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Article Synopsis
  • Spinocerebellar ataxia 27B (SCA27B) is a disease that affects balance and coordination, caused by a genetic change in a specific part of a gene called FGF14.
  • Research shows that most brain damage from this disease happens mainly in the cerebellum, which controls movement.
  • In a study of blood samples and brain tissue, scientists found that the genetic change was mostly stable over time, but it exhibited more growth in the cerebellum than in other brain areas, helping to explain why SCA27B mainly affects that part of the brain.
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Objectives: Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.

Methods: We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States.

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  • Spinocerebellar ataxia 27B (SCA27B) is an autosomal dominant disorder characterized by GAA•TTC repeat expansions that mainly cause neuronal loss in the cerebellum.
  • A study analyzing blood samples, skin cells, and brain tissues found that the repeat expansions are stable in most peripheral tissues, but significantly more unstable in specific regions of the cerebellum.
  • The cerebellar-specific expansion bias observed could help explain the disease's focused and late-onset impact on cerebellar function in affected individuals.
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  • The study investigates the factors affecting the expansion of tandem repeats, focusing on the FGF14 (GAA)·(TTC) repeat locus in a large sample of 2,530 individuals through advanced sequencing techniques.
  • Researchers discovered a prevalent 5'-flanking variant present in over 70% of alleles, which is linked to nonpathogenic alleles and the ancestral lineage of this genetic marker.
  • This common variant is associated with greater stability of the tandem repeat during inheritance and improved accessibility of chromatin, suggesting a role in preventing pathological expansion.
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  • Autosomal-dominant spinocerebellar ataxia (ADCA) caused by GAA repeat expansion in the FGF14 gene, known as SCA27B, is a common form of late-onset ataxia recently identified in Italy.
  • A study was conducted on 396 patients diagnosed with late-onset cerebellar ataxias, revealing a prevalence of 13.4% for SCA27B, with higher rates in the ADCA subgroup, and detailing various clinical features like impaired balance and gait issues.
  • The findings indicate that SCA27B results in adult-onset, slowly progressive ataxia with consistent clinical characteristics across different populations, suggesting the need for larger, multi-center
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Background: GAA-FGF14 disease/spinocerebellar ataxia 27B is a recently described neurodegenerative disease caused by (GAA) expansions in the fibroblast growth factor 14 (FGF14) gene, but its phenotypic spectrum, pathogenic threshold, and evidence-based treatability remain to be established. We report on the frequency of FGF14 (GAA) and (GAA) expansions in a large cohort of patients with idiopathic downbeat nystagmus (DBN) and their response to 4-aminopyridine.

Methods: Retrospective cohort study of 170 patients with idiopathic DBN, comprising in-depth phenotyping and assessment of 4-aminopyridine treatment response, including re-analysis of placebo-controlled video-oculography treatment response data from a previous randomised double-blind 4-aminopyridine trial.

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Background: GAA- ataxia (SCA27B) is a recently reported late-onset ataxia caused by a GAA repeat expansion in intron 1 of the gene. Initial studies revealed cerebellar atrophy in 74-97% of patients. A more detailed brain imaging characterization of GAA- ataxia is now needed to provide supportive diagnostic features and earlier disease recognition.

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A pathogenic GAA repeat expansion in the first intron of the fibroblast growth factor 14 gene (FGF14) has been recently identified as the cause of spinocerebellar ataxia 27B (SCA27B). We herein screened 160 Greek index cases with late-onset cerebellar ataxia (LOCA) for FGF14 repeat expansions using a combination of long-range PCR and bidirectional repeat-primed PCRs. We identified 19 index cases (12%) carrying a pathogenic FGF14 GAA expansion, a diagnostic yield higher than that of previously screened repeat-expansion ataxias in Greek LOCA patients.

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  • - A study involving 34 patients from Canada, France, Austria, and Australia focused on spinocerebellar ataxia 27B, highlighting the shared symptom of episodic ataxia among these individuals.
  • - The report details various episodic features experienced by the patients, indicating that the condition is not just limited to ataxia but includes other episodic symptoms as well.
  • - It was found that acetazolamide, a medication often used for ataxia, proved ineffective in treating these patients, suggesting a need for alternative therapies.
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Objectives: Intronic GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA- ataxia; SCA27B). The global epidemiology and regional prevalence of this newly reported disorder remain to be established. In this study, we investigated the frequency of GAA- ataxia in a large cohort of Brazilian patients with unsolved adult-onset ataxia.

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  • Researchers studied GAA repeat expansions in the FGF14 gene, which have been linked to spinocerebellar ataxia 27B (SCA27B), to understand its frequency and characteristics in late-onset cerebellar ataxia (LOCA) patients.
  • They screened 64 undiagnosed LOCA patients, finding that 28% had the FGF14 expansion, with gait ataxia and mild dysarthria being common symptoms.
  • The study concluded that SCA27B is the leading cause of LOCA in their patient group, suggesting FGF14 GAA expansion screening should be a standard first step in genetic testing for these patients.*
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  • About 30% of people with downbeat nystagmus (DBN) don't know why they have it, and researchers think that a genetic issue called GAA repeat expansions might be a common cause for this.
  • In a study with 170 patients, they found that 48% had these GAA repeat expansions and that patients with this genetic change had more eye and movement issues related to the brain's balance control.
  • The patients with GAA repeat expansions responded better to a treatment called 4-aminopyridine (4-AP) compared to those without, showing that this genetic cause can help doctors decide how to treat DBN.
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  • Researchers studied the SCA27B (GAA)•(TTC) repeat locus in over 2,500 individuals to understand factors leading to the expansion of tandem repeats.
  • They found a common 17-bp deletion-insertion variation that was present in about 70% of the alleles analyzed.
  • This variation was mostly found on alleles with fewer than 30 GAA repeats and contributed to increased stability during meiosis.
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  • Scientists found that a gene called FGF14, which has a part that repeats a sequence (GAA), is often related to a condition called ataxia where people have trouble with balance and coordination.
  • They studied 45 patients who had symptoms similar to another condition called CANVAS, and found that 38% of them had these GAA repeat expansions.
  • It seems that patients with these repeat expansions might have different symptoms and family histories compared to those without, suggesting it’s important to check for this when diagnosing ataxia.
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Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA-FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing.

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Ataxia due to an autosomal dominant intronic GAA repeat expansion in FGF14 [GAA-FGF14 ataxia, spinocerebellar ataxia 27B (SCA27B)] has recently been identified as one of the most common genetic late-onset ataxias. We here aimed to characterize its phenotypic profile, natural history progression, and 4-aminopyridine (4-AP) treatment response. We conducted a multi-modal cohort study of 50 GAA-FGF14 patients, comprising in-depth phenotyping, cross-sectional and longitudinal progression data (up to 7 years), MRI findings, serum neurofilament light (sNfL) levels, neuropathology, and 4-AP treatment response data, including a series of n-of-1 treatment studies.

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Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS) is caused by mutation in the SACS gene resulting in loss of function of the protein sacsin. A key feature is the formation of abnormal bundles of neurofilaments (NF) in neurons and vimentin intermediate filaments (IF) in cultured fibroblasts, suggesting a role of sacsin in IF homeostasis. Sacsin contains a J domain (SacsJ) homologous to Hsp40, that can interact with Hsp70 chaperones.

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  • Researchers identified a pathogenic GAA repeat expansion in the first intron of the gene that encodes fibroblast growth factor 14, linked to late-onset cerebellar ataxia (LOCA) in six French Canadian patients.
  • The expansion was significantly associated with LOCA in both French Canadian and German populations, indicating a strong genetic link with high odds ratios.
  • Analysis revealed that the expansion occurred in various percentages of patients from different backgrounds, and affected individuals showed reduced RNA and protein expression related to the condition.
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Glycogen storage diseases (GSDs) result from the deficiency of enzymes involved in glycogen synthesis and breakdown into glucose. Mutations in the gene PHKA2 encoding phosphorylase kinase regulatory subunit alpha 2 have been linked to GSD type IXa. We describe a family with two adult brothers with neonatal hepatosplenomegaly and later onset of hearing loss, cognitive impairment, and cerebellar involvement.

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Objective: Recessive null variants of the slow skeletal muscle troponin T1 (TNNT1) gene are a rare cause of nemaline myopathy that is fatal in infancy due to respiratory insufficiency. Muscle biopsy shows rods and fiber type disproportion. We report on 4 French Canadians with a novel form of recessive congenital TNNT1 core-rod myopathy.

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