Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

Gijs W E Santen; Emmelien Aten; Anneke T Vulto-van Silfhout; Caroline Pottinger; Bregje W M van Bon; Ivonne J H M van Minderhout; Ronelle Snowdowne; Christian A C van der Lans; Merel Boogaard; Margot M L Linssen; Linda Vijfhuizen; Michiel J R van der Wielen; M J Ellen Vollebregt; Martijn H Breuning; Marjolein Kriek; Arie van Haeringen; Johan T den Dunnen; Alexander Hoischen; Jill Clayton-Smith; Bert B A de Vries; Raoul C M Hennekam; Martine J van Belzen; Mariam Almureikhi; Anwar Baban; Mafalda Barbosa; Tawfeg Ben-Omran; Katherine Berry; Stefania Bigoni; Odile Boute; Louise Brueton; Ineke van der Burgt; Natalie Canham; Kate E Chandler; Krystyna Chrzanowska; Amanda L Collins; Teresa de Toni; John Dean; Nicolette S den Hollander; Leigh Anne Flore; Alan Fryer; Alice Gardham; John M Graham; Victoria Harrison; Denise Horn; Marjolijn C Jongmans; Dragana Josifova; Sarina G Kant; Seema Kapoor; Helen Kingston; Usha Kini; Tjitske Kleefstra; Małgorzata Krajewska-Walasek; Nancy Kramer; Saskia M Maas; Patricia Maciel; Grazia M S Mancini; Isabelle Maystadt; Shane McKee; Jeff M Milunsky; Sheela Nampoothiri; Ruth Newbury-Ecob; Sarah M Nikkel; Michael J Parker; Luis A Pérez-Jurado; Stephen P Robertson; Caroline Rooryck; Debbie Shears; Margherita Silengo; Ankur Singh; Robert Smigiel; Gabriela Soares; Miranda Splitt; Helen Stewart; Elizabeth Sweeney; May Tassabehji; Beyhan Tuysuz; Albertien M van Eerde; Catherine Vincent-Delorme; Louise C Wilson; Gozde Yesil

doi:10.1002/humu.22394

Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

Gijs W E Santen, Emmelien Aten, Anneke T Vulto-van Silfhout, Caroline Pottinger, Bregje W M van Bon, Ivonne J H M van Minderhout, Ronelle Snowdowne, Christian A C van der Lans, Merel Boogaard, Margot M L Linssen, Linda Vijfhuizen, Michiel J R van der Wielen, M J Ellen Vollebregt, Martijn H Breuning, Marjolein Kriek, Arie van Haeringen, Johan T den Dunnen, Alexander Hoischen, Jill Clayton-Smith, Bert B A de VriesRaoul C M Hennekam, Martine J van Belzen, Mariam Almureikhi (Collaborator), Anwar Baban (Collaborator), Mafalda Barbosa (Collaborator), Tawfeg Ben-Omran (Collaborator), Katherine Berry (Collaborator), Stefania Bigoni (Collaborator), Odile Boute (Collaborator), Louise Brueton (Collaborator), Ineke van der Burgt (Collaborator), Natalie Canham (Collaborator), Kate E Chandler (Collaborator), Krystyna Chrzanowska (Collaborator), Amanda L Collins (Collaborator), Teresa de Toni (Collaborator), John Dean (Collaborator), Nicolette S den Hollander (Collaborator), Leigh Anne Flore (Collaborator), Alan Fryer (Collaborator), Alice Gardham (Collaborator), John M Graham (Collaborator), Victoria Harrison (Collaborator), Denise Horn (Collaborator), Marjolijn C Jongmans (Collaborator), Dragana Josifova (Collaborator), Sarina G Kant (Collaborator), Seema Kapoor (Collaborator), Helen Kingston (Collaborator), Usha Kini (Collaborator), Tjitske Kleefstra (Collaborator), Małgorzata Krajewska-Walasek (Collaborator), Nancy Kramer (Collaborator), Saskia M Maas (Collaborator), Patricia Maciel (Collaborator), Grazia M S Mancini (Collaborator), Isabelle Maystadt (Collaborator), Shane McKee (Collaborator), Jeff M Milunsky (Collaborator), Sheela Nampoothiri (Collaborator), Ruth Newbury-Ecob (Collaborator), Sarah M Nikkel (Collaborator), Michael J Parker (Collaborator), Luis A Pérez-Jurado (Collaborator), Stephen P Robertson (Collaborator), Caroline Rooryck (Collaborator), Debbie Shears (Collaborator), Margherita Silengo (Collaborator), Ankur Singh (Collaborator), Robert Smigiel (Collaborator), Gabriela Soares (Collaborator), Miranda Splitt (Collaborator), Helen Stewart (Collaborator), Elizabeth Sweeney (Collaborator), May Tassabehji (Collaborator), Beyhan Tuysuz (Collaborator), Albertien M van Eerde (Collaborator), Catherine Vincent-Delorme (Collaborator), Louise C Wilson (Collaborator), Gozde Yesil (Collaborator)

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

Abstract

De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%). All four pathogenic variants in ARID1A appeared to be mosaic. By using all variants from the Exome Variant Server as test data, we were able to classify variants in ARID1A, ARID1B, and SMARCB1 reliably as being pathogenic or nonpathogenic. For SMARCA2, SMARCA4, and SMARCE1 several variants in the EVS remained unclassified, underlining the importance of parental testing. We have entered all variant and clinical information in LOVD-powered databases to facilitate further genotype-phenotype correlations, as these will become increasingly important because of the uptake of targeted and untargeted next generation sequencing in diagnostics. The emerging phenotype-genotype correlation is that SMARCB1 patients have the most marked physical phenotype and severe cognitive and growth delay. The variability in phenotype seems most marked in ARID1A and ARID1B patients. Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation.

Original language	English
Journal	Human Mutation
Volume	34
Issue number	11
DOIs	https://doi.org/10.1002/humu.22394
Publication status	Published - Nov 2013

Keywords

ARID1A
ARID1B
BAF
CSS
Coffin-Siris
NBS
Nicolaides-Baraitser
SMARCA2
SMARCA4
SMARCB1
SMARCE1
SWI/SNF
genotype-phenotype
mosaicism

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Santen, G. W. E., Aten, E., Vulto-van Silfhout, A. T., Pottinger, C., van Bon, B. W. M., van Minderhout, I. J. H. M., Snowdowne, R., van der Lans, C. A. C., Boogaard, M., Linssen, M. M. L., Vijfhuizen, L., van der Wielen, M. J. R., Vollebregt, M. J. E., Breuning, M. H., Kriek, M., van Haeringen, A., den Dunnen, J. T., Hoischen, A., Clayton-Smith, J., ... Yesil, G. (2013). Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients. Human Mutation, 34(11). https://doi.org/10.1002/humu.22394

@article{fab1f27254684af49c72dc73a99250a9,

title = "Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.",

abstract = "De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%). All four pathogenic variants in ARID1A appeared to be mosaic. By using all variants from the Exome Variant Server as test data, we were able to classify variants in ARID1A, ARID1B, and SMARCB1 reliably as being pathogenic or nonpathogenic. For SMARCA2, SMARCA4, and SMARCE1 several variants in the EVS remained unclassified, underlining the importance of parental testing. We have entered all variant and clinical information in LOVD-powered databases to facilitate further genotype-phenotype correlations, as these will become increasingly important because of the uptake of targeted and untargeted next generation sequencing in diagnostics. The emerging phenotype-genotype correlation is that SMARCB1 patients have the most marked physical phenotype and severe cognitive and growth delay. The variability in phenotype seems most marked in ARID1A and ARID1B patients. Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation.",

keywords = "ARID1A, ARID1B, BAF, CSS, Coffin-Siris, NBS, Nicolaides-Baraitser, SMARCA2, SMARCA4, SMARCB1, SMARCE1, SWI/SNF, genotype-phenotype, mosaicism",

author = "Santen, {Gijs W E} and Emmelien Aten and {Vulto-van Silfhout}, {Anneke T} and Caroline Pottinger and {van Bon}, {Bregje W M} and {van Minderhout}, {Ivonne J H M} and Ronelle Snowdowne and {van der Lans}, {Christian A C} and Merel Boogaard and Linssen, {Margot M L} and Linda Vijfhuizen and {van der Wielen}, {Michiel J R} and Vollebregt, {M J Ellen} and Breuning, {Martijn H} and Marjolein Kriek and {van Haeringen}, Arie and {den Dunnen}, {Johan T} and Alexander Hoischen and Jill Clayton-Smith and {de Vries}, {Bert B A} and Hennekam, {Raoul C M} and {van Belzen}, {Martine J} and Mariam Almureikhi and Anwar Baban and Mafalda Barbosa and Tawfeg Ben-Omran and Katherine Berry and Stefania Bigoni and Odile Boute and Louise Brueton and {van der Burgt}, Ineke and Natalie Canham and Chandler, {Kate E} and Krystyna Chrzanowska and Collins, {Amanda L} and {de Toni}, Teresa and John Dean and {den Hollander}, {Nicolette S} and Flore, {Leigh Anne} and Alan Fryer and Alice Gardham and Graham, {John M} and Victoria Harrison and Denise Horn and Jongmans, {Marjolijn C} and Dragana Josifova and Kant, {Sarina G} and Seema Kapoor and Helen Kingston and Usha Kini and Tjitske Kleefstra and Ma{\l}gorzata Krajewska-Walasek and Nancy Kramer and Maas, {Saskia M} and Patricia Maciel and Mancini, {Grazia M S} and Isabelle Maystadt and Shane McKee and Milunsky, {Jeff M} and Sheela Nampoothiri and Ruth Newbury-Ecob and Nikkel, {Sarah M} and Parker, {Michael J} and P{\'e}rez-Jurado, {Luis A} and Robertson, {Stephen P} and Caroline Rooryck and Debbie Shears and Margherita Silengo and Ankur Singh and Robert Smigiel and Gabriela Soares and Miranda Splitt and Helen Stewart and Elizabeth Sweeney and May Tassabehji and Beyhan Tuysuz and {van Eerde}, {Albertien M} and Catherine Vincent-Delorme and Wilson, {Louise C} and Gozde Yesil",

year = "2013",

month = nov,

doi = "10.1002/humu.22394",

language = "English",

volume = "34",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "John Wiley & Sons Ltd",

number = "11",

}

Santen, GWE, Aten, E, Vulto-van Silfhout, AT, Pottinger, C, van Bon, BWM, van Minderhout, IJHM, Snowdowne, R, van der Lans, CAC, Boogaard, M, Linssen, MML, Vijfhuizen, L, van der Wielen, MJR, Vollebregt, MJE, Breuning, MH, Kriek, M, van Haeringen, A, den Dunnen, JT, Hoischen, A, Clayton-Smith, J, de Vries, BBA, Hennekam, RCM, van Belzen, MJ, Almureikhi, M, Baban, A, Barbosa, M, Ben-Omran, T, Berry, K, Bigoni, S, Boute, O, Brueton, L, van der Burgt, I, Canham, N, Chandler, KE, Chrzanowska, K, Collins, AL, de Toni, T, Dean, J, den Hollander, NS, Flore, LA, Fryer, A, Gardham, A, Graham, JM, Harrison, V, Horn, D, Jongmans, MC, Josifova, D, Kant, SG, Kapoor, S, Kingston, H, Kini, U, Kleefstra, T, Krajewska-Walasek, M, Kramer, N, Maas, SM, Maciel, P, Mancini, GMS, Maystadt, I, McKee, S, Milunsky, JM, Nampoothiri, S, Newbury-Ecob, R, Nikkel, SM, Parker, MJ, Pérez-Jurado, LA, Robertson, SP, Rooryck, C, Shears, D, Silengo, M, Singh, A, Smigiel, R, Soares, G, Splitt, M, Stewart, H, Sweeney, E, Tassabehji, M, Tuysuz, B, van Eerde, AM, Vincent-Delorme, C, Wilson, LC & Yesil, G 2013, 'Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.', Human Mutation, vol. 34, no. 11. https://doi.org/10.1002/humu.22394

TY - JOUR

T1 - Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

AU - Santen, Gijs W E

AU - Aten, Emmelien

AU - Vulto-van Silfhout, Anneke T

AU - Pottinger, Caroline

AU - van Bon, Bregje W M

AU - van Minderhout, Ivonne J H M

AU - Snowdowne, Ronelle

AU - van der Lans, Christian A C

AU - Boogaard, Merel

AU - Linssen, Margot M L

AU - Vijfhuizen, Linda

AU - van der Wielen, Michiel J R

AU - Vollebregt, M J Ellen

AU - Breuning, Martijn H

AU - Kriek, Marjolein

AU - van Haeringen, Arie

AU - den Dunnen, Johan T

AU - Hoischen, Alexander

AU - Clayton-Smith, Jill

AU - de Vries, Bert B A

AU - Hennekam, Raoul C M

AU - van Belzen, Martine J

A2 - Almureikhi, Mariam

A2 - Baban, Anwar

A2 - Barbosa, Mafalda

A2 - Ben-Omran, Tawfeg

A2 - Berry, Katherine

A2 - Bigoni, Stefania

A2 - Boute, Odile

A2 - Brueton, Louise

A2 - van der Burgt, Ineke

A2 - Canham, Natalie

A2 - Chandler, Kate E

A2 - Chrzanowska, Krystyna

A2 - Collins, Amanda L

A2 - de Toni, Teresa

A2 - Dean, John

A2 - den Hollander, Nicolette S

A2 - Flore, Leigh Anne

A2 - Fryer, Alan

A2 - Gardham, Alice

A2 - Graham, John M

A2 - Harrison, Victoria

A2 - Horn, Denise

A2 - Jongmans, Marjolijn C

A2 - Josifova, Dragana

A2 - Kant, Sarina G

A2 - Kapoor, Seema

A2 - Kingston, Helen

A2 - Kini, Usha

A2 - Kleefstra, Tjitske

A2 - Krajewska-Walasek, Małgorzata

A2 - Kramer, Nancy

A2 - Maas, Saskia M

A2 - Maciel, Patricia

A2 - Mancini, Grazia M S

A2 - Maystadt, Isabelle

A2 - McKee, Shane

A2 - Milunsky, Jeff M

A2 - Nampoothiri, Sheela

A2 - Newbury-Ecob, Ruth

A2 - Nikkel, Sarah M

A2 - Parker, Michael J

A2 - Pérez-Jurado, Luis A

A2 - Robertson, Stephen P

A2 - Rooryck, Caroline

A2 - Shears, Debbie

A2 - Silengo, Margherita

A2 - Singh, Ankur

A2 - Smigiel, Robert

A2 - Soares, Gabriela

A2 - Splitt, Miranda

A2 - Stewart, Helen

A2 - Sweeney, Elizabeth

A2 - Tassabehji, May

A2 - Tuysuz, Beyhan

A2 - van Eerde, Albertien M

A2 - Vincent-Delorme, Catherine

A2 - Wilson, Louise C

A2 - Yesil, Gozde

PY - 2013/11

Y1 - 2013/11

N2 - De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%). All four pathogenic variants in ARID1A appeared to be mosaic. By using all variants from the Exome Variant Server as test data, we were able to classify variants in ARID1A, ARID1B, and SMARCB1 reliably as being pathogenic or nonpathogenic. For SMARCA2, SMARCA4, and SMARCE1 several variants in the EVS remained unclassified, underlining the importance of parental testing. We have entered all variant and clinical information in LOVD-powered databases to facilitate further genotype-phenotype correlations, as these will become increasingly important because of the uptake of targeted and untargeted next generation sequencing in diagnostics. The emerging phenotype-genotype correlation is that SMARCB1 patients have the most marked physical phenotype and severe cognitive and growth delay. The variability in phenotype seems most marked in ARID1A and ARID1B patients. Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation.

AB - De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%). All four pathogenic variants in ARID1A appeared to be mosaic. By using all variants from the Exome Variant Server as test data, we were able to classify variants in ARID1A, ARID1B, and SMARCB1 reliably as being pathogenic or nonpathogenic. For SMARCA2, SMARCA4, and SMARCE1 several variants in the EVS remained unclassified, underlining the importance of parental testing. We have entered all variant and clinical information in LOVD-powered databases to facilitate further genotype-phenotype correlations, as these will become increasingly important because of the uptake of targeted and untargeted next generation sequencing in diagnostics. The emerging phenotype-genotype correlation is that SMARCB1 patients have the most marked physical phenotype and severe cognitive and growth delay. The variability in phenotype seems most marked in ARID1A and ARID1B patients. Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation.

KW - ARID1A

KW - ARID1B

KW - BAF

KW - CSS

KW - Coffin-Siris

KW - NBS

KW - Nicolaides-Baraitser

KW - SMARCA2

KW - SMARCA4

KW - SMARCB1

KW - SMARCE1

KW - SWI/SNF

KW - genotype-phenotype

KW - mosaicism

U2 - 10.1002/humu.22394

DO - 10.1002/humu.22394

M3 - Article

C2 - 23929686

SN - 1059-7794

VL - 34

JO - Human Mutation

JF - Human Mutation

IS - 11

ER -

Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

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