TY - JOUR
T1 - De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome
AU - Rivière, Jean Baptiste
AU - Van Bon, Bregje W.M.
AU - Hoischen, Alexander
AU - Kholmanskikh, Stanislav S.
AU - O'Roak, Brian J.
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.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84859430859
U2 - 10.1038/ng.1091
DO - 10.1038/ng.1091
M3 - Article
C2 - 22366783
AN - SCOPUS:84859430859
SN - 1061-4036
VL - 44
SP - 440
EP - 444
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -