De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

Jean Baptiste Rivière, Bregje W M Van Bon, Alexander Hoischen, Stanislav S. Kholmanskikh, Brian O'Roak, Christian Gilissen, Sabine Gijsen, Christopher T. Sullivan, Susan L. Christian, Omar A. Abdul-Rahman, Joan F. Atkin, Nicolas Chassaing, Valerie Drouin-Garraud, Andrew E. Fry, Jean Pierre Fryns, Karen W. Gripp, Marlies Kempers, Tjitske Kleefstra, Grazia M S Mancini, Małgorzata J M NowaczykConny M A Van Ravenswaaij-Arts, Tony Roscioli, Michael Marble, Jill A. Rosenfeld, Victoria M. Siu, Bert B A De Vries, Jay Shendure, Alain Verloes, Joris A. Veltman, Han G. Brunner, M. Elizabeth Ross, Daniela T. Pilz, William B. Dobyns

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic acting-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes.

Original languageEnglish (US)
Pages (from-to)440-444
Number of pages5
JournalNature Genetics
Volume44
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

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Actins
Exome
Mutation
Genes
Genetic Fitness
Coloboma
Developmental Disabilities
Phenotype
Clark-Baraitser syndrome
Brain
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Rivière, J. B., Van Bon, B. W. M., Hoischen, A., Kholmanskikh, S. S., O'Roak, B., Gilissen, C., ... Dobyns, W. B. (2012). De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nature Genetics, 44(4), 440-444. https://doi.org/10.1038/ng.1091

De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. / Rivière, Jean Baptiste; Van Bon, Bregje W M; Hoischen, Alexander; Kholmanskikh, Stanislav S.; O'Roak, Brian; Gilissen, Christian; Gijsen, Sabine; Sullivan, Christopher T.; Christian, Susan L.; Abdul-Rahman, Omar A.; Atkin, Joan F.; Chassaing, Nicolas; Drouin-Garraud, Valerie; Fry, Andrew E.; Fryns, Jean Pierre; Gripp, Karen W.; Kempers, Marlies; Kleefstra, Tjitske; Mancini, Grazia M S; Nowaczyk, Małgorzata J M; Van Ravenswaaij-Arts, Conny M A; Roscioli, Tony; Marble, Michael; Rosenfeld, Jill A.; Siu, Victoria M.; De Vries, Bert B A; Shendure, Jay; Verloes, Alain; Veltman, Joris A.; Brunner, Han G.; Ross, M. Elizabeth; Pilz, Daniela T.; Dobyns, William B.

In: Nature Genetics, Vol. 44, No. 4, 04.2012, p. 440-444.

Research output: Contribution to journalArticle

Rivière, JB, Van Bon, BWM, Hoischen, A, Kholmanskikh, SS, O'Roak, B, Gilissen, C, Gijsen, S, Sullivan, CT, Christian, SL, Abdul-Rahman, OA, Atkin, JF, Chassaing, N, Drouin-Garraud, V, Fry, AE, Fryns, JP, Gripp, KW, Kempers, M, Kleefstra, T, Mancini, GMS, Nowaczyk, MJM, Van Ravenswaaij-Arts, CMA, Roscioli, T, Marble, M, Rosenfeld, JA, Siu, VM, De Vries, BBA, Shendure, J, Verloes, A, Veltman, JA, Brunner, HG, Ross, ME, Pilz, DT & Dobyns, WB 2012, 'De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome', Nature Genetics, vol. 44, no. 4, pp. 440-444. https://doi.org/10.1038/ng.1091
Rivière JB, Van Bon BWM, Hoischen A, Kholmanskikh SS, O'Roak B, Gilissen C et al. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nature Genetics. 2012 Apr;44(4):440-444. https://doi.org/10.1038/ng.1091
Rivière, Jean Baptiste ; Van Bon, Bregje W M ; Hoischen, Alexander ; Kholmanskikh, Stanislav S. ; O'Roak, Brian ; Gilissen, Christian ; Gijsen, Sabine ; Sullivan, Christopher T. ; Christian, Susan L. ; Abdul-Rahman, Omar A. ; Atkin, Joan F. ; Chassaing, Nicolas ; Drouin-Garraud, Valerie ; Fry, Andrew E. ; Fryns, Jean Pierre ; Gripp, Karen W. ; Kempers, Marlies ; Kleefstra, Tjitske ; Mancini, Grazia M S ; Nowaczyk, Małgorzata J M ; Van Ravenswaaij-Arts, Conny M A ; Roscioli, Tony ; Marble, Michael ; Rosenfeld, Jill A. ; Siu, Victoria M. ; De Vries, Bert B A ; Shendure, Jay ; Verloes, Alain ; Veltman, Joris A. ; Brunner, Han G. ; Ross, M. Elizabeth ; Pilz, Daniela T. ; Dobyns, William B. / De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. In: Nature Genetics. 2012 ; Vol. 44, No. 4. pp. 440-444.
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AU - O'Roak, Brian

AU - Gilissen, Christian

AU - Gijsen, Sabine

AU - Sullivan, Christopher T.

AU - Christian, Susan L.

AU - Abdul-Rahman, Omar A.

AU - Atkin, Joan F.

AU - Chassaing, Nicolas

AU - Drouin-Garraud, Valerie

AU - Fry, Andrew E.

AU - Fryns, Jean Pierre

AU - Gripp, Karen W.

AU - Kempers, Marlies

AU - Kleefstra, Tjitske

AU - Mancini, Grazia M S

AU - Nowaczyk, Małgorzata J M

AU - Van Ravenswaaij-Arts, Conny M A

AU - Roscioli, Tony

AU - Marble, Michael

AU - Rosenfeld, Jill A.

AU - Siu, Victoria M.

AU - De Vries, Bert B A

AU - Shendure, Jay

AU - Verloes, Alain

AU - Veltman, Joris A.

AU - Brunner, Han G.

AU - Ross, M. Elizabeth

AU - Pilz, Daniela T.

AU - Dobyns, William B.

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