ArticleAmerican journal of human genetics2022
Recessive PRDM13 mutations cause fatal perinatal brainstem dysfunction with cerebellar hypoplasia and disrupt Purkinje cell differentiation.
Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Classic "PCH" Genes are a Rare Cause of Radiologic Pontocerebellar Hypoplasia.Cerebellum (London, England) · 2024Pooled it
- Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech.Molecular autism · 2025Trial
- Genetic Insights in Hindbrain Abnormalities Through Network Analysis Expose Key Biological Pathways in Hindbrain Development.Cerebellum (London, England) · 2025Article
- PRDM13 is required for specification of PAX2 lineage inhibitory neurons in the developing cerebellum.Developmental biology · 2025Article
- Biallelic MED29 variants cause pontocerebellar hypoplasia with cataracts.European journal of human genetics : EJHG · 2025Article
- A zinc finger-dependent, PRDM13-driven mechanism regulates retinal progenitor cell fate from mouse embryonic stem cells via WNT signaling.Stem cell reports · 2025Article
- Conference Report: Cerebellar Development and Disease at Single-Cell Resolution.Cerebellum (London, England) · 2025Article
- Mapping the developmental profile of ventricular zone-derived neurons in the human cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetic modeling of degenerative diseases and mechanisms of neuronal regeneration in the zebrafish cerebellum.Cellular and molecular life sciences : CMLS · 2024Review
- Human organoid model of pontocerebellar hypoplasia 2a recapitulates brain region-specific size differences.Disease models & mechanisms · 2024Article
- Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review.BMC medical genomics · 2024Article
- Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site ofMolecular vision · 2024Article
- Revisiting the development of cerebellar inhibitory interneurons in the light of single-cell genetic analyses.Histochemistry and cell biology · 2024Review
- A non-coding variant in the Kozak sequence of RARS2 strongly decreases protein levels and causes pontocerebellar hypoplasia.BMC medical genomics · 2023Article
- The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.Scientific reports · 2022Article
- Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy.American journal of human genetics · 2022Article
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Authors and funding
27 authors at 10 institutions in 3 countries.
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Abstract
Pontocerebellar hypoplasias (PCHs) are congenital disorders characterized by hypoplasia or early atrophy of the cerebellum and brainstem, leading to a very limited motor and cognitive development. Although over 20 genes have been shown to be mutated in PCHs, a large proportion of affected individuals remains undiagnosed. We describe four families with children presenting with severe neonatal brainstem dysfunction and pronounced deficits in cognitive and motor development associated with four different bi-allelic mutations in PRDM13, including homozygous truncating variants in the most severely affected individuals. Brain MRI and fetopathological examination revealed a PCH-like phenotype, associated with major hypoplasia of inferior olive nuclei and dysplasia of the dentate nucleus. Notably, histopathological examinations highlighted a sparse and disorganized Purkinje cell layer in the cerebellum. PRDM13 encodes a transcriptional repressor known to be critical for neuronal subtypes specification in the mouse retina and spinal cord but had not been implicated, so far, in hindbrain development. snRNA-seq data mining and in situ hybridization in humans show that PRDM13 is expressed at early stages in the progenitors of the cerebellar ventricular zone, which gives rise to cerebellar GABAergic neurons, including Purkinje cells. We also show that loss of function of prdm13 in zebrafish leads to a reduction in Purkinje cells numbers and a complete absence of the inferior olive nuclei. Altogether our data identified bi-allelic mutations in PRDM13 as causing a olivopontocerebellar hypoplasia syndrome and suggest that early deregulations of the transcriptional control of neuronal fate specification could contribute to a significant number of cases.
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