Cargando…
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...
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Elsevier
2021
|
| Materias: | |
| 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 |
| _version_ | 1784632573927882752 |
|---|---|
| author | 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. |
| author_facet | 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. |
| author_sort | Laboy Cintron, Dianne |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-8756495 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Elsevier |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-87564952022-01-18 A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay 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. HGG Adv Report 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. Elsevier 2021-11-25 /pmc/articles/PMC8756495/ /pubmed/35047857 http://dx.doi.org/10.1016/j.xhgg.2021.100072 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| spellingShingle | Report 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. A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay |
| title | A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay |
| title_full | A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay |
| title_fullStr | A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay |
| title_full_unstemmed | A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay |
| title_short | A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay |
| title_sort | recurrent, de novo pathogenic variant in arpc4 disrupts actin filament formation and causes microcephaly and speech delay |
| topic | Report |
| url | 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 |
| work_keys_str_mv | AT laboycintrondianne arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT muiralisonm arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT scottabbey arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT mcdonaldmarie arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT monaghankristing arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT santiagosimteresa arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT wentzenseningridm arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT delucachiara arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT brancatifrancesco arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT harrisdavidj arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT gouelicecilia arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT stottmannrolf arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT pradacarlose arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT bidermanwaberskimarta arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT meffordheatherc arecurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT laboycintrondianne recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT muiralisonm recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT scottabbey recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT mcdonaldmarie recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT monaghankristing recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT santiagosimteresa recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT wentzenseningridm recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT delucachiara recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT brancatifrancesco recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT harrisdavidj recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT gouelicecilia recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT stottmannrolf recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT pradacarlose recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT bidermanwaberskimarta recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay AT meffordheatherc recurrentdenovopathogenicvariantinarpc4disruptsactinfilamentformationandcausesmicrocephalyandspeechdelay |