A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay

We report seven affected individuals from six families with a recurrent, de novo variant in the ARPC4 gene (c.472C>T [p.Arg158Cys (GenBank: NM_005718.4)]). Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment. ARPC4 is a core subunit of...

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Detalles Bibliográficos
Autores principales: Laboy Cintron, Dianne, Muir, Alison M., Scott, Abbey, McDonald, Marie, Monaghan, Kristin G., Santiago-Sim, Teresa, Wentzensen, Ingrid M., De Luca, Chiara, Brancati, Francesco, Harris, David J., Goueli, Cecilia, Stottmann, Rolf, Prada, Carlos E., Biderman Waberski, Marta, Mefford, Heather C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756495/
https://www.ncbi.nlm.nih.gov/pubmed/35047857
http://dx.doi.org/10.1016/j.xhgg.2021.100072
Descripción
Sumario:We report seven affected individuals from six families with a recurrent, de novo variant in the ARPC4 gene (c.472C>T [p.Arg158Cys (GenBank: NM_005718.4)]). Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment. ARPC4 is a core subunit of the actin-related protein (ARP2/3) complex, which catalyzes the formation of F-actin networks. We show that the recurrent ARPC4 missense change is associated with a decreased amount of F-actin in cells from two affected individuals. Taken together, our results implicate heterozygous ARPC4 missense variants as a cause of neurodevelopmental disorders and microcephaly.

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