We delineate GOT2 deficiency, expanding the malate–aspartate shuttle (MAS) spectrum as a developmental & epileptic encephalopathy (DEE). It clarifies routes to diagnosis/therapy, placing GOT2 alongside rare recessive DEEs from SLC25A12 & MDH1/2 as inborn MAS disorders. @uclqsion.bsky.social

📣New from Pujol & colleagues! 📄Bi-allelic variants in the ribosomal protein RPS6KC1 cause a complex neurodevelopmental disorder

Our EPG5 study shows a continuum: early neurodevelopmental disruption and adult-onset neurodegeneration, both tied by autophagy defects. Like GBA1, PLA2G6, WDR45 & SYNJ1, PSMF1, EPG5 links rare paediatric disorders to adult PD/dementia. Rare informing common. bit.ly/432N7LT @UCLIoN @UCLBrainScience

New international collaborative work incl. our group @erasmusmc.bsky.social on MACF1 published @ajhgnews.bsky.social A clinical and genotype-phenotype analysis of MACF1 variants www.sciencedirect.com/science/arti... #raredisease #genetics

Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons

Our new study characterises ELFN1 deficiency as a novel autosomal recessive neurodevelopmental disorder marked by epilepsy, GDD/ID, & movement disorders. Biallelic ELFN1 variants disrupt synaptic protein trafficking to the cell surface—validated through functional assays and mouse/zebrafish models.

We define the recessive ELOVL1-related disorder, part of an emerging group of neurocutaneous syndromes caused by biallelic ELOVL1/4 variants. Monoallelic ELOVL1/4/5 variants lead to spastic paraplegia & ataxia. These genes encode enzymes that elongate very-long-chain fatty acids. loom.ly/wwx-XQ4

The dystonin gene encodes three major isoforms: DST-a, -b, and -e. Jacob et al. report that variants exclusively affecting DST-b cause an autosomal recessive congenital myopathy, while variants that also affect DST-a cause a lethal contracture syndrome. tinyurl.com/3p99pu9j

We define the critical role of the LGI1–ADAM22/23 pathway in developmental & epileptic encephalopathy (DEE)—essential for regulating synaptic transmission and brain excitability. Previously linked ADAM22 to DEE, now we report ultra-rare biallelic LGI1 & ADAM23 variants causing lethal DEE.

Loss of XRCC1 disrupts cerebellar development in zebrafish due to toxic PARP1 accumulation. Strikingly, parp1 knockdown rescues the XRCC1 phenotype, supporting PARP1 inhibition as a potential therapy in recessive XRCC1-related neurodegenerative disorders with ataxia. www.nature.com/articles/s41...

Proud to present our work identifying a role for DIAPH1 and gamma-actin in regulating DSB repair and how defects in this pathway give rise to human disease. Big thanks to everyone involved, especially Beth Woodward, Sudipta Lahiri and @anoopsinghchauhan.bsky.social. www.nature.com/articles/s41...

We previously reported a novel recessive pediatric neurodegenerative disorder linked to BORCS8. Now, we identify another BORC complex subunit, BORCS5, as a new disease gene causing a broader neurodevelopmental & neurodegenerative spectrum with clear genotype–phenotype correlation. Read the preprint:

📣New from @rdexeter.bsky.social & co! 📄Bi-allelic UGGT1 variants cause a congenital disorder of glycosylation

Our lab characterises the autosomal recessive TRMT1-related neurodevelopmental disorder through a large cohort, patient-derived cells, and zebrafish model—linking defective tRNA methylation to intellectual disability and expanding the emerging group of "tRNAopathies". www.cell.com/ajhg/fulltex...

📣Online now! 📄Bi-allelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency

For #RareDiseaseDay2025, @qs-neurogenetics.bsky.social is celebrating the invaluable contributions of our international collaborators, whose dedication is driving ground-breaking advancements in rare disease research across the globe. ucl.ac.uk/ion/news/202...

Prof. Shamima Rahman comments on ‘Biallelic NDUFA13 variants lead to a neurodevelopmental phenotype with gradual neurological impairment’ by Kaiyrzhanov et al, highlighting NDUFA13 deficiency in Leigh syndrome, linking neuroinflammation & imaging. Please read at: buff.ly/3D5Dtyf

As part of 2 parallel studies, we delineated a new subtype of neurodevelopmental disorder linked to biallelic GTF3C3 variants. One study models the disorder using zebrafish, while the other utilizes fly. Check both papers below: academic.oup.com/braincomms/a... www.sciencedirect.com/science/arti...

NDUFA13, a mitochondrial complex I subunit, was linked to complex I deficiency in only 3 patients. We now report 10 more cases, expanding the phenotypic spectrum, consolidating its role, & comparing it with other complex I deficiency subtypes. Please Check our paper: academic.oup.com/braincomms/a...

In 2013, we identified KPTN as a cause of NDD, though its function was unclear at the time. By 2017, it was shown to be part of the KICSTOR complex with KICS2, ITFG2, & SZT2, regulating mTORC1 signaling. We've now published KICS2 linked to NDD, with ITFG2 next in line. www.cell.com/ajhg/fulltex...

TRMT1 & TRMT1L modify tRNAs, essential for protein production. Their modifications are crucial for tRNA stability & function. Biallelic TRMT1 variants are linked to intellectual disability, while TRMT1L variants lead to a neurodegenerative disorder. Check our new paper! www.cell.com/cell-reports...

We report 35 patients with biallelic RBL2 loss-of-function variants presenting with developmental delay/intellectual disability, hypotonia, seizures, microcephaly & brain abnormalities. Drosophila models recapitulate key features & suggest RBL2 re-expression may help rescue neurological symptoms.

In 2021, we identified a rare VWA1 founder mutation in UK & Western European populations, linked to neuromuscular disorder but elusive due to low genomic coverage. We now report an expanded phenotypic spectrum in a global cohort with this recurrent mutation & other VWA1 variants.

Clinical and Molecular Characterisation of SLC31A1-Related Neurodevelopmental Disorder. www.medrxiv.org/content/10.1...

Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish https://www.biorxiv.org/content/10.1101/2024.11.25.625242v1

Pioneering genomic insights into rare pediatric neurological diseases in Central Asia & Transcaucasia! Our Nature Genetics correspondence highlights the CAT-Genomics consortium's impact in underrepresented regions, advancing diagnoses & novel discoveries. bit.ly/3V6lUE3