Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

JKJ Van Houdt; BA Nowakowska; SB Sousa; BDC van Schaik; E Seuntjens; N Avonce; A Sifrim; OA Abdul-Rahman; MJH van den Boogaard; A Bottani; M Castori; V Cormier-Daire; MA Deardorff; I Filges; A Fryer; JP Fryns; S Gana; L Garavelli; G Gillessen-Kaesbach; BD Hall; D Horn; Danny Huylebroeck; J Klapecki; M Krajewska-Walasek; A Kuechler; MA Lines; S Maas; KD MacDermot; S Mckee; A Magee; Stella Man; Y Moreau; F Morice-Picard; E Obersztyn; J Pilch; E Rosser; N Shannon; I Stolte-Dijkstra; P Van Dijck; C Vilain; Alain Vogels; E Wakeling; D Wieczorek; L Wilson; O Zuffardi; AHC van Kampen; K DeVriendt; R Hennekam; JR Vermeesch

doi:10.1038/ng.1105

Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

JKJ Van Houdt, BA Nowakowska, SB Sousa, BDC van Schaik, E Seuntjens, N Avonce, A Sifrim, OA Abdul-Rahman, MJH van den Boogaard, A Bottani, M Castori, V Cormier-Daire, MA Deardorff, I Filges, A Fryer, JP Fryns, S Gana, L Garavelli, G Gillessen-Kaesbach, BD HallD Horn, Danny Huylebroeck, J Klapecki, M Krajewska-Walasek, A Kuechler, MA Lines, S Maas, KD MacDermot, S Mckee, A Magee, Stella Man, Y Moreau, F Morice-Picard, E Obersztyn, J Pilch, E Rosser, N Shannon, I Stolte-Dijkstra, P Van Dijck, C Vilain, Alain Vogels, E Wakeling, D Wieczorek, L Wilson, O Zuffardi, AHC van Kampen, K DeVriendt, R Hennekam, JR Vermeesch

Clinical Genetics

Research output: Contribution to journal › Article › Academic › peer-review

194 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	Undefined/Unknown
Pages (from-to)	445-U261
Journal	Nature Genetics
Volume	44
Issue number	4
DOIs	https://doi.org/10.1038/ng.1105
Publication status	Published - 2012

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EMC MGC-02-96-01

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10.1038/ng.1105

http://hdl.handle.net/1765/56989

Cite this

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., ... Vermeesch, JR. (2012). Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nature Genetics, 44(4), 445-U261. 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}, JKJ and BA Nowakowska and SB Sousa and {van Schaik}, BDC and E Seuntjens and N Avonce and A Sifrim and OA Abdul-Rahman and {van den Boogaard}, MJH and A Bottani and M Castori and V Cormier-Daire and MA Deardorff and I Filges and A Fryer and JP Fryns and S Gana and L Garavelli and G Gillessen-Kaesbach and BD Hall and D Horn and Danny Huylebroeck and J Klapecki and M Krajewska-Walasek and A Kuechler and MA Lines and S Maas and KD MacDermot and S Mckee and A Magee and Stella Man and Y Moreau and F Morice-Picard and E Obersztyn and J Pilch and E Rosser and N Shannon and I Stolte-Dijkstra and {Van Dijck}, P and C Vilain and Alain Vogels and E Wakeling and D Wieczorek and L Wilson and O Zuffardi and {van Kampen}, AHC and K DeVriendt and R Hennekam and JR Vermeesch",

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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, Man, S, 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-U261. https://doi.org/10.1038/ng.1105

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

AU - Van Houdt, JKJ

AU - Nowakowska, BA

AU - Sousa, SB

AU - van Schaik, BDC

AU - Seuntjens, E

AU - Avonce, N

AU - Sifrim, A

AU - Abdul-Rahman, OA

AU - van den Boogaard, MJH

AU - Bottani, A

AU - Castori, M

AU - Cormier-Daire, V

AU - Deardorff, MA

AU - Filges, I

AU - Fryer, A

AU - Fryns, JP

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AU - Garavelli, L

AU - Gillessen-Kaesbach, G

AU - Hall, BD

AU - Horn, D

AU - Huylebroeck, Danny

AU - Klapecki, J

AU - Krajewska-Walasek, M

AU - Kuechler, A

AU - Lines, MA

AU - Maas, S

AU - MacDermot, KD

AU - Mckee, S

AU - Magee, A

AU - Man, Stella

AU - Moreau, Y

AU - Morice-Picard, F

AU - Obersztyn, E

AU - Pilch, J

AU - Rosser, E

AU - Shannon, N

AU - Stolte-Dijkstra, I

AU - Van Dijck, P

AU - Vilain, C

AU - Vogels, Alain

AU - Wakeling, E

AU - Wieczorek, D

AU - Wilson, L

AU - Zuffardi, O

AU - van Kampen, AHC

AU - DeVriendt, K

AU - Hennekam, R

AU - Vermeesch, JR

PY - 2012

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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.

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DO - 10.1038/ng.1105

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