Matthis Synofzik

SynTEF1 restores the functional disease phenotype of SCA27B in an hiPSC-derived neuronal model

This study shows that SynTEF1 restores FGF14 expression and neuronal function in SCA27B patient-derived neurons.

Cerebrospinal fluid YWHAG:NPTX2 ratio predicts clinical severity and future phenoconversion in frontotemporal lobar degeneration

The paper identifies the CSF YWHAG:NPTX2 ratio as a biomarker for predicting clinical severity and phenoconversion in FTLD, showing strong correlation with disease progression and improved trial design potential.

Machine-learning MRI stratification of genetic frontotemporal dementia for clinical trial enrichment

This paper uses machine learning to stratify genetic frontotemporal dementia patients into subtypes and provides progression scores that improve trial enrichment efficiency.

Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders

This study identifies digenic inheritance of SPG7 and AFG3L2 mutations as a cause of motor neuron and cerebellar disorders in 17 patients.

Standardized transcriptome analysis improves rare disease diagnosis in the pan-European Solve-RD consortium

The paper presents a standardized RNA-seq analysis framework for rare disease diagnosis, identifying molecular diagnoses in 7.7% of previously undiagnosed cases.

Distinct TAF15 amyloid filament folds define multiple subtypes of FTLD-TAF15

This study identifies distinct TAF15 amyloid filament structures in different FTLD-FET subtypes, leading to the renaming of the disease group as FTLD-TAF15.

MRI-based classifier to identify close-to-onset cases in C9orf72 genetic frontotemporal dementia

The paper develops an MRI-based machine learning classifier to identify presymptomatic C9orf72 carriers at high risk of disease onset within two years.

Screening rare genetic diagnoses for amenability to bespoke antisense oligonucleotide therapy development: a retrospective cohort study

The paper estimates the proportion of genetic diagnoses in a pediatric cohort that are amenable to antisense oligonucleotide therapy, finding 4.9% eligible or likely eligible.

White Matter Hyperintensities Precede other Biomarkers in GRN Frontotemporal Dementia

The paper shows that white matter hyperintensities (WMHs) appear before other biomarkers in GRN-related frontotemporal dementia, suggesting they are early indicators of disease progression.

A Core Pattern of Cerebellar and Brainstem Degeneration and Reduced Cerebrocerebellar Structural Covariance in Spinocerebellar Ataxia Type 3 (SCA3): MRI Volumetrics from ENIGMA-Ataxia

This study uses MRI volumetrics to analyze cerebellar and brainstem degeneration in SCA3, finding consistent atrophy patterns and reduced cerebrocerebellar covariance.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing

This study identifies genetic risk factors for FTLD-TDP subtypes using whole-genome sequencing and meta-analysis across multiple cohorts.

Most L1CAM is not associated with extracellular vesicles in human biofluids and iPSC-derived neurons

The paper validates EV isolation from multiple biofluids using orthogonal methods but finds L1CAM does not reliably enrich for neuron-derived EVs.

Consensus guidelines for eligibility assessment of pathogenic variants to antisense oligonucleotide treatments

The paper presents consensus guidelines for assessing pathogenic variants' eligibility for antisense oligonucleotide treatments, including classification criteria and considerations for different therapeutic approaches.

Comprehensive reanalysis for CNVs in exome sequencing data from unsolved rare disease cases results in new diagnoses

The paper reanalyzes exome sequencing data from rare disease cases to identify previously undetected copy number variants, resulting in diagnoses for 51 families and partial explanations for 34 individuals.

The Pattern and Staging of Brain Atrophy in Spinocerebellar Ataxia Type 2 (SCA2): MRI Volumetrics from ENIGMA-Ataxia

This study uses MRI volumetrics to characterize brain atrophy patterns in SCA2, finding progressive degeneration starting in cerebellar white matter and spreading to other brain regions.

Advancing molecular, phenotypic and mechanistic insights of FGF14 pathogenic expansions (SCA27B)

This study identifies the complete sequences of pathogenic and non-pathogenic FGF14 repeat expansions in patients with cerebellar ataxia, revealing a lower pathogenic threshold and providing mechanistic insights into disease causation.

A common flanking variant is associated with enhanced meiotic stability of the FGF14-SCA27B locus

The paper identifies a common flanking variant linked to increased meiotic stability at the FGF14-SCA27B repeat locus.

Unravelling undiagnosed rare disease cases by HiFi long-read genome sequencing

The paper uses HiFi long-read sequencing to identify genetic variants in undiagnosed rare disease families, finding novel diagnoses in 13% of cases and candidate variants in 4.3%.

Small non-coding RNA content in plasma-derived extracellular vesicles distinguish ataxic SCA3 mutation carriers from pre-ataxic and control subjects

Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia

The paper develops and validates a strategy to detect FGF14 GAA repeat expansions using PCR and Sanger sequencing, showing comparable accuracy to nanopore sequencing and suitable for clinical use.

Neuropathy target esterase activity predicts retinopathy among PNPLA6 disorders

The paper identifies NTE activity as a biomarker for retinopathy and endocrinopathy in PNPLA6 disorders, using clinical and preclinical data to establish a genotype-activity-phenotype relationship.

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

This study investigates the association between cerebellar and subcortical atrophy and neuropsychiatric symptoms in genetic frontotemporal dementia, finding significant differences across genetic mutations.

Blood neurofilament light chain levels are associated with disease progression in a transgenic SCA3 mouse model

The paper measures blood neurofilament light chain (NfL) levels in a transgenic SCA3 mouse model and finds they correlate with disease progression and severity.

Global network structure and local transcriptomic vulnerability shape atrophy in sporadic and genetic behavioral variant frontotemporal dementia

This study shows that atrophy patterns in bvFTD are shaped by both global brain network structure and local transcriptomic vulnerability from disease-related genes.

Intrinsic neural timescales related to sensory processing: Evidence from abnormal behavioural states

The paper investigates intrinsic neural timescales in different behavioural states and finds that sensory deficits are associated with prolonged neural timescales, while motor deficits do not show such changes.

Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia

The paper investigates the relationship between gene expression and brain atrophy in genetic frontotemporal dementia, finding correlations between atrophy patterns and specific gene sets related to vascular, glial, and neuronal functions.

Data-driven algorithm for the diagnosis of behavioral variant frontotemporal dementia

The paper develops a random forest classifier to diagnose behavioral variant frontotemporal dementia using MRI and cognitive scores, achieving high accuracy in both training and validation cohorts.

The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension

This study shows that low oxygen tension promotes SOD1 misfolding and aggregation in ALS-related cells, linking oxygen levels to disease pathogenesis.