Henry Houlden

RAPID: A Targeted Long-Read RNA Workflow for Functional Resolution of Splicing Variants in Rare Disease

RAPID uses targeted long-read RNA sequencing to resolve splice variants in rare disease cases, providing functional evidence for diagnosis and variant interpretation.

Loss of RUBCN causes autophagy overdrive in a neurodevelopmental disorder with age-dependent neurodegeneration

This study identifies RUBCN variants in neurodevelopmental disorders and shows they cause autophagy overdrive, leading to neurodegeneration.

Deep Brain Stimulation Microelectrodes as a Source of Human Subcortical RNA: Validation of a Low-Input Transcriptomic Protocol

This paper validates a low-input RNA extraction protocol using DBS microelectrodes to obtain subcortical RNA from post-mortem brains, confirming brain origin and sub-regional cellular identity.

Equivalent Gain-of-Function Variants in KCNK3 and KCNK9 and their Contribution to Distinct TASK K2P Channelopathies

The paper identifies equivalent gain-of-function variants in KCNK3 and KCNK9 that cause distinct channelopathies and investigates their functional effects on homomeric and heteromeric TASK channels.

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort

This study identifies pathogenic and intermediate repeat expansions in Parkinson's disease and parkinsonism across 11 ancestries, highlighting ATXN2's role in PD risk and ancestry-specific patterns.

Characterization of a novel neurodevelopmental rare disease caused by a mutation within the autophagy gene ATG9B

The paper reports a novel neurodevelopmental disorder caused by a frameshift mutation in ATG9B, and characterizes its effects using cell models and knock-in mice.

iPSC-derived extracellular vesicles rescue deficits in human and mouse models of Parkinsons disease

The paper shows that extracellular vesicles from healthy iPSCs can reverse Parkinson's disease-related deficits in human and mouse models.

Dimerisation and twist reversal of the Lewy fold in α-synuclein mutants with Parkinson's disease and dementia

The paper reports the structures of α-synuclein filaments from individuals with Parkinson's disease and dementia, revealing differences in dimerisation and twist reversal between pathogenic and non-pathogenic variants.

A 5' UTR CCG expansion in TBC1D7 causes oculopharyngodistal myopathy

The paper identifies a CCG expansion in TBC1D7 as a cause of oculopharyngodistal myopathy, showing variable repeat structure and epigenetic regulation.

Bi-allelic ATG12 variants impair autophagy and cause a neurodevelopmental disorder

The paper identifies bi-allelic ATG12 variants causing a neurodevelopmental disorder by impairing autophagy, with clinical and functional evidence from patient cells, yeast, and zebrafish models.

Human promoter analysis of the Programmed Axon Death genes NMNAT2 and SARM1

The paper identifies promoter variants in NMNAT2 and SARM1 that affect their transcription levels and may contribute to susceptibility to Programmed Axon Death.

BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy

This study identifies BLOC1S1 variants causing a hypomyelinating leukodystrophy with epileptic encephalopathy, showing impaired lysosomal and autophagic function.

MDGA2 homozygous loss-of-function variants cause developmental and epileptic encephalopathy

This study identifies homozygous loss-of-function MDGA2 variants in individuals with developmental and epileptic encephalopathy, establishing MDGA2 as a novel gene for this condition.

A transposase-derived gene required for human brain development

This study identifies PGBD5 as a transposase-derived gene essential for brain development in humans and mice, with deficiency causing intellectual disability and seizures.

CIZ1-LOSS CAUSES FEMALE-SPECIFIC AUTOSOMAL NEURODEVELOPMENTAL DISORDER THROUGH DEFECTIVE X-INACTIVATION MAINTENANCE

The paper identifies a female-specific neurodevelopmental disorder caused by biallelic CIZ1 loss-of-function variants, which disrupt X-chromosome inactivation maintenance.

CANVAS causing AAGGG repeat expansions cause tissue-specific reduction in RFC1 expression and increase sensitivity to DNA damage

Large-scale genetic characterization of Parkinson's disease in the African and African admixed populations

This study identifies genetic variants associated with Parkinson's disease in African and African admixed populations, highlighting differences from European and Asian populations.

The LRRK2 p.A419V variant associates with risk of Parkinson disease in the East Asian population and an evaluation on age of onset

The paper identifies the LRRK2 p.A419V variant as a significant risk factor for Parkinson's disease in East Asian populations and explores its association with age of onset.

The Global Landscape of Genetic Variation in Parkinson's disease: Multi-Ancestry Insights into Established Disease Genes and their Translational Relevance

This paper analyzes genetic variation in Parkinson's disease across multiple ancestries, revealing ancestry-specific patterns and highlighting the importance of diverse populations in genetic research.

Bi-allelic mutations in KCTD11 cause a new form of autosomal recessive intermediate Charcot-Marie-Tooth disease

This paper identifies bi-allelic mutations in KCTD11 as a cause of autosomal recessive intermediate Charcot-Marie-Tooth disease and elucidates its role in myelin homeostasis through molecular mechanisms.

The Ethnic/Racial Variations of Intracerebral Hemorrhage Genetics (ERICH-GENE) Study Protocol

ERICH-GENE collects and analyzes genomic and neuroimaging data from over 10,000 multi-ethnic ICH cases to identify genetic risk factors and trans-ethnic variation in ICH.

Independent Generation of Amyloid-β via Novel APP Transcripts

The paper identifies novel APP transcripts that generate Aβ independently of β-secretase, showing their expression and presence in CSF.

Biallelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a syndromic neurodevelopmental disorder

This study identifies biallelic TRMT1 variants causing a syndromic neurodevelopmental disorder through tRNA modification defects in humans and zebrafish.

Metabolic remodelling in hiPSC-derived myofibres carrying the m.3243A>G mutation

This study generates hiPSC-derived myofibres with the m.3243A>G mutation to model mitochondrial disease, showing metabolic and physiological changes related to mutation load.

Molecular and cellular signatures differentiate Parkinson's disease from Parkinson's disease with dementia

This study compares molecular and cellular signatures of Parkinson's disease and Parkinson's disease with dementia using single-nuclear transcriptomics, finding distinct gene expression patterns and biological pathways.

Biallelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.

RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS

The paper identifies SPOUT1/CENP-32 as a causative gene for SpADMiSS, linking its dysfunction to mitotic spindle defects and neurodevelopmental disorders.

Transcriptomic analysis of repeat expansion-ataxias uncovers distinct non-neuronal cell type-specific signatures of disease across the human brain

This study uses bulk and single nuclear RNA-sequencing to analyze transcriptomic changes in repeat expansion ataxias, revealing distinct non-neuronal cell type-specific disease signatures across the human brain.

Human TRMT1 and TRMT1L paralogs ensure the proper modification state, stability, and function of tRNAs

The paper identifies the roles of TRMT1 and TRMT1L in tRNA modifications, showing their impact on tRNA stability and function, and links TRMT1 variants to disease.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1

The paper identifies a non-coding risk variant in GBA1 associated with Parkinson's disease in African ancestry populations, showing it disrupts splicing and reduces glucocerebrosidase activity.