Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

Jeroen K.J. Van Houdt; Beata Anna Nowakowska; Sérgio B. Sousa; Barbera D.C. Van Schaik; Eve Seuntjens; Nelson Avonce; Alejandro Sifrim; Omar A. Abdul-Rahman; Marie José H. Van Den Boogaard; Armand Bottani; Marco Castori; Valérie Cormier-Daire; Matthew A. Deardorff; Isabel Filges; Alan Fryer; Jean Pierre Fryns; Simone Gana; Livia Garavelli; Gabriele Gillessen-Kaesbach; Bryan D. Hall; Denise Horn; Danny Huylebroeck; Jakub Klapecki; Malgorzata Krajewska-Walasek; Alma Kuechler; Matthew A. Lines; Saskia Maas; Kay D. MacDermot; Shane McKee; Alex Magee; Stella A. De Man; Yves Moreau; Fanny Morice-Picard; Ewa Obersztyn; Jacek Pilch; Elizabeth Rosser; Nora Shannon; Irene Stolte-Dijkstra; Patrick Van Dijck; Catheline Vilain; Annick Vogels; Emma Wakeling; Dagmar Wieczorek; Louise Wilson; Orsetta Zuffardi; Antoine H.C. Van Kampen; Koenraad Devriendt; Raoul Hennekam; Joris Robert Vermeesch

doi:10.1038/ng.1105

Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

Jeroen K.J. Van Houdt, Beata Anna Nowakowska, Sérgio B. Sousa, Barbera D.C. Van Schaik, Eve Seuntjens, Nelson Avonce, Alejandro Sifrim, Omar A. Abdul-Rahman, Marie José H. Van Den Boogaard, Armand Bottani, Marco Castori, Valérie Cormier-Daire, Matthew A. Deardorff, Isabel Filges, Alan Fryer, Jean Pierre Fryns, Simone Gana, Livia Garavelli, Gabriele Gillessen-Kaesbach, Bryan D. HallDenise Horn, Danny Huylebroeck, Jakub Klapecki, Malgorzata Krajewska-Walasek, Alma Kuechler, Matthew A. Lines, Saskia Maas, Kay D. MacDermot, Shane McKee, Alex Magee, Stella A. De Man, Yves Moreau, Fanny Morice-Picard, Ewa Obersztyn, Jacek Pilch, Elizabeth Rosser, Nora Shannon, Irene Stolte-Dijkstra, Patrick Van Dijck, Catheline Vilain, Annick Vogels, Emma Wakeling, Dagmar Wieczorek, Louise Wilson, Orsetta Zuffardi, Antoine H.C. Van Kampen, Koenraad Devriendt, Raoul Hennekam^*, Joris Robert Vermeesch

^*Corresponding author for this work

Institute of Human Genetics

210 Citations (Scopus)

Abstract

Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available. SMARCA2 encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling complex that is involved in the regulation of gene transcription. The mutations cluster within sequences that encode ultra-conserved motifs in the catalytic ATPase region of the protein. These alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity. The identification of SMARCA2 mutations in humans provides insight into the function of the Snf2 helicase family.

Original language	English
Journal	Nature Genetics
Volume	44
Issue number	4
Pages (from-to)	445-449
Number of pages	5
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.1105
Publication status	Published - 01.04.2012

Funding

We thank the Genome of the Netherlands Project (GoNL) for providing their variant data. GoNL is one of the rainbow projects of the Dutch hub of the Biobanking and Biomolecular Research Infrastructure (BBMRI-NL). We thank S. Olabarriaga and M. Santcroos for their support in using the Dutch Grid for data analysis. We thank T.J.L. de Ravel and P. Brady for critical reading of the manuscript and G. Peeters for technical support. We are grateful to the subjects and their families for participating in this study. This work was made possible by grants from the Agency for Innovation by Science and Technology (IWT; SBO-60848), the Catholic University of Leuven (PFV/10/016 SymBioSys and GOA/12/015 to J.R.V., Y.M. and K.D.), the Queen Elisabeth Medical Foundation (GSKE 1113 to D. Hu and E.S.) and the type 3 large-infrastructure support InfraMouse by the Flanders Hercules Foundation (to D. Hu). B.A.N. is supported by a KOLUMB fellowship from the Foundation for Polish Science. S.B.S. was supported by the Fundação Para a Ciência e Tecnologia (SFRH/ BD/46778/2008).

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Van Houdt, J. K. J., Nowakowska, B. A., Sousa, S. B., Van Schaik, B. D. C., Seuntjens, E., Avonce, N., Sifrim, A., Abdul-Rahman, O. A., Van Den Boogaard, M. J. H., Bottani, A., Castori, M., Cormier-Daire, V., Deardorff, M. A., Filges, I., Fryer, A., Fryns, J. P., Gana, S., Garavelli, L., Gillessen-Kaesbach, G., ... Vermeesch, J. R. (2012). Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nature Genetics, 44(4), 445-449. https://doi.org/10.1038/ng.1105

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title = "Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome",

abstract = "Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available. SMARCA2 encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling complex that is involved in the regulation of gene transcription. The mutations cluster within sequences that encode ultra-conserved motifs in the catalytic ATPase region of the protein. These alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity. The identification of SMARCA2 mutations in humans provides insight into the function of the Snf2 helicase family.",

author = "\{Van Houdt\}, \{Jeroen K.J.\} and Nowakowska, \{Beata Anna\} and Sousa, \{S{\'e}rgio B.\} and \{Van Schaik\}, \{Barbera D.C.\} and Eve Seuntjens and Nelson Avonce and Alejandro Sifrim and Abdul-Rahman, \{Omar A.\} and \{Van Den Boogaard\}, \{Marie Jos{\'e} H.\} and Armand Bottani and Marco Castori and Val{\'e}rie Cormier-Daire and Deardorff, \{Matthew A.\} and Isabel Filges and Alan Fryer and Fryns, \{Jean Pierre\} and Simone Gana and Livia Garavelli and Gabriele Gillessen-Kaesbach and Hall, \{Bryan D.\} and Denise Horn and Danny Huylebroeck and Jakub Klapecki and Malgorzata Krajewska-Walasek and Alma Kuechler and Lines, \{Matthew A.\} and Saskia Maas and MacDermot, \{Kay D.\} and Shane McKee and Alex Magee and \{De Man\}, \{Stella A.\} and Yves Moreau and Fanny Morice-Picard and Ewa Obersztyn and Jacek Pilch and Elizabeth Rosser and Nora Shannon and Irene Stolte-Dijkstra and \{Van Dijck\}, Patrick and Catheline Vilain and Annick Vogels and Emma Wakeling and Dagmar Wieczorek and Louise Wilson and Orsetta Zuffardi and \{Van Kampen\}, \{Antoine H.C.\} and Koenraad Devriendt and Raoul Hennekam and Vermeesch, \{Joris Robert\}",

year = "2012",

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day = "1",

doi = "10.1038/ng.1105",

language = "English",

volume = "44",

pages = "445--449",

journal = "Nature Genetics",

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Van Houdt, JKJ, Nowakowska, BA, Sousa, SB, Van Schaik, BDC, Seuntjens, E, Avonce, N, Sifrim, A, Abdul-Rahman, OA, Van Den Boogaard, MJH, Bottani, A, Castori, M, Cormier-Daire, V, Deardorff, MA, Filges, I, Fryer, A, Fryns, JP, Gana, S, Garavelli, L, Gillessen-Kaesbach, G, Hall, BD, Horn, D, Huylebroeck, D, Klapecki, J, Krajewska-Walasek, M, Kuechler, A, Lines, MA, Maas, S, MacDermot, KD, McKee, S, Magee, A, De Man, SA, Moreau, Y, Morice-Picard, F, Obersztyn, E, Pilch, J, Rosser, E, Shannon, N, Stolte-Dijkstra, I, Van Dijck, P, Vilain, C, Vogels, A, Wakeling, E, Wieczorek, D, Wilson, L, Zuffardi, O, Van Kampen, AHC, Devriendt, K, Hennekam, R & Vermeesch, JR 2012, 'Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome', Nature Genetics, vol. 44, no. 4, pp. 445-449. https://doi.org/10.1038/ng.1105

TY - JOUR

T1 - Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

AU - Van Houdt, Jeroen K.J.

AU - Nowakowska, Beata Anna

AU - Sousa, Sérgio B.

AU - Van Schaik, Barbera D.C.

AU - Seuntjens, Eve

AU - Avonce, Nelson

AU - Sifrim, Alejandro

AU - Abdul-Rahman, Omar A.

AU - Van Den Boogaard, Marie José H.

AU - Bottani, Armand

AU - Castori, Marco

AU - Cormier-Daire, Valérie

AU - Deardorff, Matthew A.

AU - Filges, Isabel

AU - Fryer, Alan

AU - Fryns, Jean Pierre

AU - Gana, Simone

AU - Garavelli, Livia

AU - Gillessen-Kaesbach, Gabriele

AU - Hall, Bryan D.

AU - Horn, Denise

AU - Huylebroeck, Danny

AU - Klapecki, Jakub

AU - Krajewska-Walasek, Malgorzata

AU - Kuechler, Alma

AU - Lines, Matthew A.

AU - Maas, Saskia

AU - MacDermot, Kay D.

AU - McKee, Shane

AU - Magee, Alex

AU - De Man, Stella A.

AU - Moreau, Yves

AU - Morice-Picard, Fanny

AU - Obersztyn, Ewa

AU - Pilch, Jacek

AU - Rosser, Elizabeth

AU - Shannon, Nora

AU - Stolte-Dijkstra, Irene

AU - Van Dijck, Patrick

AU - Vilain, Catheline

AU - Vogels, Annick

AU - Wakeling, Emma

AU - Wieczorek, Dagmar

AU - Wilson, Louise

AU - Zuffardi, Orsetta

AU - Van Kampen, Antoine H.C.

AU - Devriendt, Koenraad

AU - Hennekam, Raoul

AU - Vermeesch, Joris Robert

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available. SMARCA2 encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling complex that is involved in the regulation of gene transcription. The mutations cluster within sequences that encode ultra-conserved motifs in the catalytic ATPase region of the protein. These alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity. The identification of SMARCA2 mutations in humans provides insight into the function of the Snf2 helicase family.

AB - Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available. SMARCA2 encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling complex that is involved in the regulation of gene transcription. The mutations cluster within sequences that encode ultra-conserved motifs in the catalytic ATPase region of the protein. These alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity. The identification of SMARCA2 mutations in humans provides insight into the function of the Snf2 helicase family.

UR - https://www.scopus.com/pages/publications/84859423484

U2 - 10.1038/ng.1105

DO - 10.1038/ng.1105

M3 - Journal articles

C2 - 22366787

AN - SCOPUS:84859423484

SN - 1061-4036

VL - 44

SP - 445

EP - 449

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

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