Update on the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome

Nataliya Di Donato, Alma Kuechler, Samantha Vergano, Wolfram Heinritz, Joann Bodurtha, Sabiha R. Merchant, Galen Breningstall, Roger Ladda, Susan Sell, Janine Altmüller, Nina Bögershausen, Andrew E. Timms, Karl Hackmann, Evelin Schrock, Sarah Collins, Carissa Olds, Andreas Rump, William B. Dobyns

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Baraitser–Winter cerebrofrontofacial syndrome is caused by heterozygous missense mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1. Recently, we characterized the large cohort of 41 patients presenting with this condition. Our series contained 34 patients with mutations in ACTB and only nine with ACTG1 mutations. Here, we report on seven unrelated patients with six mutations in ACTG1–four novel and two previously reported. Only one of seven patients was clinically diagnosed with this disorder and underwent ACTB/ACTG1 targeted sequencing, four patients were screened as a part of the large lissencephaly cohort and two were tested with exome sequencing. Retrospectively, facial features were compatible with the diagnosis but significantly milder than previously reported in four patients, and non-specific in one. The pattern of malformations of cortical development was highly similar in four of six patients with available MRI images and encompassed frontal predominant pachygyria merging with the posterior predominant band heterotopia. Two remaining patients showed mild involvement consistent with bilaterally simplified gyration over the frontal lobes. Taken together, we expand the clinical spectrum of the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations.

Original languageEnglish (US)
Pages (from-to)2644-2651
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Volume170
Issue number10
DOIs
StatePublished - Oct 1 2016

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Lissencephaly
Mutation
Exome
Malformations of Cortical Development
Cerebrofrontofacial Syndrome
Frontal Lobe
Missense Mutation
Actins
Brain
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Di Donato, N., Kuechler, A., Vergano, S., Heinritz, W., Bodurtha, J., Merchant, S. R., ... Dobyns, W. B. (2016). Update on the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome. American Journal of Medical Genetics, Part A, 170(10), 2644-2651. https://doi.org/10.1002/ajmg.a.37771
Di Donato, Nataliya ; Kuechler, Alma ; Vergano, Samantha ; Heinritz, Wolfram ; Bodurtha, Joann ; Merchant, Sabiha R. ; Breningstall, Galen ; Ladda, Roger ; Sell, Susan ; Altmüller, Janine ; Bögershausen, Nina ; Timms, Andrew E. ; Hackmann, Karl ; Schrock, Evelin ; Collins, Sarah ; Olds, Carissa ; Rump, Andreas ; Dobyns, William B. / Update on the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome. In: American Journal of Medical Genetics, Part A. 2016 ; Vol. 170, No. 10. pp. 2644-2651.
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Di Donato, N, Kuechler, A, Vergano, S, Heinritz, W, Bodurtha, J, Merchant, SR, Breningstall, G, Ladda, R, Sell, S, Altmüller, J, Bögershausen, N, Timms, AE, Hackmann, K, Schrock, E, Collins, S, Olds, C, Rump, A & Dobyns, WB 2016, 'Update on the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome', American Journal of Medical Genetics, Part A, vol. 170, no. 10, pp. 2644-2651. https://doi.org/10.1002/ajmg.a.37771

Update on the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome. / Di Donato, Nataliya; Kuechler, Alma; Vergano, Samantha; Heinritz, Wolfram; Bodurtha, Joann; Merchant, Sabiha R.; Breningstall, Galen; Ladda, Roger; Sell, Susan; Altmüller, Janine; Bögershausen, Nina; Timms, Andrew E.; Hackmann, Karl; Schrock, Evelin; Collins, Sarah; Olds, Carissa; Rump, Andreas; Dobyns, William B.

In: American Journal of Medical Genetics, Part A, Vol. 170, No. 10, 01.10.2016, p. 2644-2651.

Research output: Contribution to journalArticle

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T1 - Update on the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome

AU - Di Donato, Nataliya

AU - Kuechler, Alma

AU - Vergano, Samantha

AU - Heinritz, Wolfram

AU - Bodurtha, Joann

AU - Merchant, Sabiha R.

AU - Breningstall, Galen

AU - Ladda, Roger

AU - Sell, Susan

AU - Altmüller, Janine

AU - Bögershausen, Nina

AU - Timms, Andrew E.

AU - Hackmann, Karl

AU - Schrock, Evelin

AU - Collins, Sarah

AU - Olds, Carissa

AU - Rump, Andreas

AU - Dobyns, William B.

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Y1 - 2016/10/1

N2 - Baraitser–Winter cerebrofrontofacial syndrome is caused by heterozygous missense mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1. Recently, we characterized the large cohort of 41 patients presenting with this condition. Our series contained 34 patients with mutations in ACTB and only nine with ACTG1 mutations. Here, we report on seven unrelated patients with six mutations in ACTG1–four novel and two previously reported. Only one of seven patients was clinically diagnosed with this disorder and underwent ACTB/ACTG1 targeted sequencing, four patients were screened as a part of the large lissencephaly cohort and two were tested with exome sequencing. Retrospectively, facial features were compatible with the diagnosis but significantly milder than previously reported in four patients, and non-specific in one. The pattern of malformations of cortical development was highly similar in four of six patients with available MRI images and encompassed frontal predominant pachygyria merging with the posterior predominant band heterotopia. Two remaining patients showed mild involvement consistent with bilaterally simplified gyration over the frontal lobes. Taken together, we expand the clinical spectrum of the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations.

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Di Donato N, Kuechler A, Vergano S, Heinritz W, Bodurtha J, Merchant SR et al. Update on the ACTG1-associated Baraitser–Winter cerebrofrontofacial syndrome. American Journal of Medical Genetics, Part A. 2016 Oct 1;170(10):2644-2651. https://doi.org/10.1002/ajmg.a.37771