5q31 duplications encompassing PURA are associated with a neurodevelopmental disorder
Abstract
PURA heterozygous microdeletions and pathogenic variants have been previously associated with neurodevelopmental disorders (NDDs), grouped into PURA-NDDs, characterized by severe neonatal hypotonia, feeding difficulties, developmental delay, intellectual disability, epilepsy, and distinctive facial features. Here we report four individuals carrying overlapping 5q31 duplications encompassing PURA, in addition to five cases from the DECIPHER database and one previously described in the literature. All patients share common features including developmental delay and mild to moderate intellectual disability. The minimal region of overlap spans 215 kb and contains only the PURA gene, suggesting PURA as the candidate gene underlying the observed phenotype. Using transcriptomic and biochemical analyses on cultured lymphocytes from one patient, we found that 5q31 duplication causes a significant upregulation of PURA mRNA and PURA protein, respectively. RNA Sequencing also revealed dysregulated expression of various genes involved in human pathology, especially in neurodevelopmental disorders characterized by intellectual disability. Using primary hippocampal neuronal cultures from mouse embryos, we demonstrated that PURA overexpression impairs neuronal morphology in vitro, inducing a reduction in dendritic arborization and in dendritic spine density. Our findings support that 5q31 duplications encompassing PURA represent a novel genomic disorder presenting with a milder phenotype than the reciprocal deletion syndrome and implicate PURA dosage dysregulation as a key contributor to the associated clinical features.
Related
- MED20 biallelic pathogenic variants cause a neurodevelopmental disorder altering both transcription activity and Transcription-Coupled Repair pathway
- Turning Red to Green Repeatedly: Ancestral LWS Duplications Drive Convergent Visual Tuning in Teleost Fishes.
- Internet-delivered cognitive behavioral therapy is associated with distinct blood small RNA profiles in panic disorder
- Spliceosome defects and neurodevelopmental disorders
- HNRNPH2-R114W remodels RNA splicing and neurodevelopmental gene programs in isogenic cerebral organoids
BibTeX
@article{challeat20265q31,
title = {{5q31 duplications encompassing PURA are associated with a neurodevelopmental disorder}},
author = {Laurine Challeat and Solène Remize and Tarek Alouane and David Laurenceau and Chloé Boisseau and Catherine Hubert and Noémie Celton and Nathalie Le Du and Sandrine Vonwill and Camille Gevrin and Lara Kerbellec and Céline Pebrel-Richard and Matthieu Egloff and Caroline Navarro and Isabelle Perthus and Tanguy Niclass and Roseline Caumes and Jade Fauqueux and Médéric Jeanne and Thomas Smol and Frédéric Laumonnier and Marie-Laure Vuillaume},
journal = {European Journal of Human Genetics},
year = {2026},
month = sep,
doi = {10.1038/s41431-026-02230-7},
url = {https://hal.science/hal-05761223v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - 5q31 duplications encompassing PURA are associated with a neurodevelopmental disorder
AU - Laurine Challeat
AU - Solène Remize
AU - Tarek Alouane
AU - David Laurenceau
AU - Chloé Boisseau
AU - Catherine Hubert
AU - Noémie Celton
AU - Nathalie Le Du
AU - Sandrine Vonwill
AU - Camille Gevrin
AU - Lara Kerbellec
AU - Céline Pebrel-Richard
AU - Matthieu Egloff
AU - Caroline Navarro
AU - Isabelle Perthus
AU - Tanguy Niclass
AU - Roseline Caumes
AU - Jade Fauqueux
AU - Médéric Jeanne
AU - Thomas Smol
AU - Frédéric Laumonnier
AU - Marie-Laure Vuillaume
PY - 2026
DA - 2026/09/22
JO - European Journal of Human Genetics
DO - 10.1038/s41431-026-02230-7
UR - https://hal.science/hal-05761223v1
AB - PURA heterozygous microdeletions and pathogenic variants have been previously associated with neurodevelopmental disorders (NDDs), grouped into PURA-NDDs, characterized by severe neonatal hypotonia, feeding difficulties, developmental delay, intellectual disability, epilepsy, and distinctive facial features. Here we report four individuals carrying overlapping 5q31 duplications encompassing PURA, in addition to five cases from the DECIPHER database and one previously described in the literature. All patients share common features including developmental delay and mild to moderate intellectual disability. The minimal region of overlap spans 215 kb and contains only the PURA gene, suggesting PURA as the candidate gene underlying the observed phenotype. Using transcriptomic and biochemical analyses on cultured lymphocytes from one patient, we found that 5q31 duplication causes a significant upregulation of PURA mRNA and PURA protein, respectively. RNA Sequencing also revealed dysregulated expression of various genes involved in human pathology, especially in neurodevelopmental disorders characterized by intellectual disability. Using primary hippocampal neuronal cultures from mouse embryos, we demonstrated that PURA overexpression impairs neuronal morphology in vitro, inducing a reduction in dendritic arborization and in dendritic spine density. Our findings support that 5q31 duplications encompassing PURA represent a novel genomic disorder presenting with a milder phenotype than the reciprocal deletion syndrome and implicate PURA dosage dysregulation as a key contributor to the associated clinical features.
SN - 1018-4813
SN - 1476-5438
ER -