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

ABSTRACT: 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.

SUBMITTER: Laboy Cintron D

PROVIDER: S-EPMC8756495 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Laboy Cintron Dianne D Muir Alison M AM Scott Abbey A McDonald Marie M Monaghan Kristin G KG Santiago-Sim Teresa T Wentzensen Ingrid M IM De Luca Chiara C Brancati Francesco F Harris David J DJ Goueli Cecilia C Stottmann Rolf R Prada Carlos E CE Biderman Waberski Marta M Mefford Heather C HC

HGG advances 20211125 1

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-ac ...[more]

PMID: 35047857

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