A Novel TAF1C Missense Variant Causes Neurodevelopmental Regression via Disrupted Nucleolar Localization and Nucleoplasmic Aggregation DOI
S Rehan Ahmad,

Nimish Vijayakumar,

Nazim Nasir

et al.

Clinical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

ABSTRACT TAF1C (TATA box‐binding protein‐associated factor, RNA polymerase I subunit C) is an essential component of the transcription machinery responsible for ribosomal synthesis and nucleolar function. Variants in have recently emerged as rare genetic causes early‐onset neurological syndromes characterized by stress impaired ribosome biogenesis, leading to developmental delay brain atrophy. Here, we report a novel homozygous missense variant (c.1766C>T; p.Ser589Leu) 3‐year 8‐month‐old boy who exhibited normal development until age two, followed generalized seizures progressive neurodevelopmental regression, spasticity, microcephaly, cerebellar MRI revealed asymmetric diffusion restriction diffuse Although mutant transcript protein were expressed at levels peripheral blood cells, immunofluorescence analysis loss localization formation abnormal thread‐like aggregates within nucleoplasm. These findings suggest that p.Ser589Leu disease through functional mislocalization rather than expression. Our case expands phenotypic mechanistic spectrum ‐related disorders highlights importance proper subnuclear maintaining neuronal function development.

Language: Английский

Repeated behavioural evolution is associated with convergence of gene expression in cavity-nesting songbirds DOI
Sara E. Lipshutz, Mark S. Hibbins, Alexandra B. Bentz

et al.

Nature Ecology & Evolution, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Language: Английский

Citations

1
A Novel TAF1C Missense Variant Causes Neurodevelopmental Regression via Disrupted Nucleolar Localization and Nucleoplasmic Aggregation DOI
S Rehan Ahmad,

Nimish Vijayakumar,

Nazim Nasir

et al.

Clinical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

ABSTRACT TAF1C (TATA box‐binding protein‐associated factor, RNA polymerase I subunit C) is an essential component of the transcription machinery responsible for ribosomal synthesis and nucleolar function. Variants in have recently emerged as rare genetic causes early‐onset neurological syndromes characterized by stress impaired ribosome biogenesis, leading to developmental delay brain atrophy. Here, we report a novel homozygous missense variant (c.1766C>T; p.Ser589Leu) 3‐year 8‐month‐old boy who exhibited normal development until age two, followed generalized seizures progressive neurodevelopmental regression, spasticity, microcephaly, cerebellar MRI revealed asymmetric diffusion restriction diffuse Although mutant transcript protein were expressed at levels peripheral blood cells, immunofluorescence analysis loss localization formation abnormal thread‐like aggregates within nucleoplasm. These findings suggest that p.Ser589Leu disease through functional mislocalization rather than expression. Our case expands phenotypic mechanistic spectrum ‐related disorders highlights importance proper subnuclear maintaining neuronal function development.

Language: Английский

Citations

0