Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort

Pleuntje J. van der Sluijs; Marieke Joosten; Caroline Alby; Tania Attié-Bitach; Kelly Gilmore; Christele Dubourg; Mélanie Fradin; Tianyun Wang; Evangeline C. Kurtz-Nelson; Kaitlyn P. Ahlers; Peer Arts; Christopher P. Barnett; Myla Ashfaq; Anwar Baban; Myrthe van den Born; Sarah Borrie; Tiffany Busa; Alicia Byrne; Miriam Carriero; Claudia Cesario; Karen Chong; Anna Maria Cueto-González; Jennifer C. Dempsey; Karin E.M. Diderich; Dan Doherty; Stense Farholt; Erica H. Gerkes; Svetlana Gorokhova; Lutgarde C.P. Govaerts; Pernille A. Gregersen; Scott E. Hickey; Mathilde Lefebvre; Francesca Mari; Jelena Martinovic; Hope Northrup; Melanie O'Leary; Kareesma Parbhoo; Sophie Patrier; Bernt Popp; Fernando Santos-Simarro; Corinna Stoltenburg; Christel Thauvin-Robinet; Elisabeth Thompson; Anneke T. Vulto-van Silfhout; Farah R. Zahir; Hamish S. Scott; Rachel K. Earl; Evan E. Eichler; Neeta L. Vora; Yael Wilnai; Jessica L. Giordano; Ronald J. Wapner; Jill A. Rosenfeld; Monique C. Haak; Gijs W.E. Santen

doi:10.1016/j.gim.2022.04.010

Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort

Pleuntje J. van der Sluijs, Marieke Joosten, Caroline Alby, Tania Attié-Bitach, Kelly Gilmore, Christele Dubourg, Mélanie Fradin, Tianyun Wang, Evangeline C. Kurtz-Nelson, Kaitlyn P. Ahlers, Peer Arts, Christopher P. Barnett, Myla Ashfaq, Anwar Baban, Myrthe van den Born, Sarah Borrie, Tiffany Busa, Alicia Byrne, Miriam Carriero, Claudia CesarioKaren Chong, Anna Maria Cueto-González, Jennifer C. Dempsey, Karin E.M. Diderich, Dan Doherty, Stense Farholt, Erica H. Gerkes, Svetlana Gorokhova, Lutgarde C.P. Govaerts, Pernille A. Gregersen, Scott E. Hickey, Mathilde Lefebvre, Francesca Mari, Jelena Martinovic, Hope Northrup, Melanie O'Leary, Kareesma Parbhoo, Sophie Patrier, Bernt Popp, Fernando Santos-Simarro, Corinna Stoltenburg, Christel Thauvin-Robinet, Elisabeth Thompson, Anneke T. Vulto-van Silfhout, Farah R. Zahir, Hamish S. Scott, Rachel K. Earl, Evan E. Eichler, Neeta L. Vora, Yael Wilnai, Jessica L. Giordano, Ronald J. Wapner, Jill A. Rosenfeld, Monique C. Haak, Gijs W.E. Santen^*

^*Corresponding author for this work

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

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Abstract

Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes.

Methods: Clinical data was collected through an extensive web-based survey.

Results: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%).

Conclusion: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.

Original language	English
Pages (from-to)	1753-1760
Number of pages	8
Journal	Genetics in Medicine
Volume	24
Issue number	8
DOIs	https://doi.org/10.1016/j.gim.2022.04.010
Publication status	Published - Aug-2022

Keywords

ARID1A
ARID1B BAFopathy
BAF-complex
Fetal
SMARCA4
SMARCB1

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10.1016/j.gim.2022.04.010

Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohortFinal publisher's version, 445 KBLicence: Taverne

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van der Sluijs, P. J., Joosten, M., Alby, C., Attié-Bitach, T., Gilmore, K., Dubourg, C., Fradin, M., Wang, T., Kurtz-Nelson, E. C., Ahlers, K. P., Arts, P., Barnett, C. P., Ashfaq, M., Baban, A., van den Born, M., Borrie, S., Busa, T., Byrne, A., Carriero, M., ... Santen, G. W. E. (2022). Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort. Genetics in Medicine, 24(8), 1753-1760. https://doi.org/10.1016/j.gim.2022.04.010

@article{c3db25c40cef46758d5209e165a6c832,

title = "Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort",

abstract = "Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes.Methods: Clinical data was collected through an extensive web-based survey.Results: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%).Conclusion: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.",

keywords = "ARID1A, ARID1B BAFopathy, BAF-complex, Fetal, SMARCA4, SMARCB1",

author = "{van der Sluijs}, {Pleuntje J.} and Marieke Joosten and Caroline Alby and Tania Atti{\'e}-Bitach and Kelly Gilmore and Christele Dubourg and M{\'e}lanie Fradin and Tianyun Wang and Kurtz-Nelson, {Evangeline C.} and Ahlers, {Kaitlyn P.} and Peer Arts and Barnett, {Christopher P.} and Myla Ashfaq and Anwar Baban and {van den Born}, Myrthe and Sarah Borrie and Tiffany Busa and Alicia Byrne and Miriam Carriero and Claudia Cesario and Karen Chong and Cueto-Gonz{\'a}lez, {Anna Maria} and Dempsey, {Jennifer C.} and Diderich, {Karin E.M.} and Dan Doherty and Stense Farholt and Gerkes, {Erica H.} and Svetlana Gorokhova and Govaerts, {Lutgarde C.P.} and Gregersen, {Pernille A.} and Hickey, {Scott E.} and Mathilde Lefebvre and Francesca Mari and Jelena Martinovic and Hope Northrup and Melanie O'Leary and Kareesma Parbhoo and Sophie Patrier and Bernt Popp and Fernando Santos-Simarro and Corinna Stoltenburg and Christel Thauvin-Robinet and Elisabeth Thompson and {Vulto-van Silfhout}, {Anneke T.} and Zahir, {Farah R.} and Scott, {Hamish S.} and Earl, {Rachel K.} and Eichler, {Evan E.} and Vora, {Neeta L.} and Yael Wilnai and Giordano, {Jessica L.} and Wapner, {Ronald J.} and Rosenfeld, {Jill A.} and Haak, {Monique C.} and Santen, {Gijs W.E.}",

note = "Funding Information: Sequencing and analysis of cases 5 and 18 was funded by the National Institute of Child Human Development (Grant Nos. K23 HD088742 and R01 HD105868 [to N.L.V.]). Funding Information: This work was supported, in part, by grants from the National Institutes of Health (Grant No. R01 MH101221 [to E.E.E.]). E.E.E. is an investigator of the Howard Hughes Medical Institute. Funding Information: Sequencing and analysis for individual 30 was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute , the National Eye Institute , and the National Heart, Lung, and Blood Institute (Grant Nos. UM1 HG008900 and R01 HG009141 ). Funding Information: We would like to thank Ileana Minguel for her assistance in the collection of patient data and Aude Tessier and Anne-Claire Brehin for referring cases and conducting genetic analysis. This work was supported, in part, by grants from the National Institutes of Health (Grant No. R01 MH101221 [to E.E.E.]). E.E.E. is an investigator of the Howard Hughes Medical Institute. Sequencing and analysis for individual 30 was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute (Grant Nos. UM1 HG008900 and R01 HG009141). Sequencing and analysis of cases 5 and 18 was funded by the National Institute of Child Human Development (Grant Nos. K23 HD088742 and R01 HD105868 [to N.L.V.]). Conceptualization: P.J.v.d.S. G.W.E.S.; Data Curation: P.J.v.d.S. G.W.E.S.; Formal Analysis: P.J.v.d.S. G.W.E.S.; Funding Acquisition: M.O. E.E.E. N.L.V. G.W.E.S.; Investigation: P.J.v.d.S. G.W.E.S.; Methodology: P.J.v.d.S. G.W.E.S.; Project Administration: P.J.v.d.S.; Resources: P.J.v.d.S. M.J. C.A. T.A.-B. K.G. C.D. M.F. T.W. E.C.K.-N. K.P.A. P.A. C.P.B. M.A. A.Ba. M.v.d.B. S.B. T.B. A.By. M.C. C.C. K.C. A.M.C.-G. J.C.D. K.E.M.D. D.D. S.F. E.H.G. S.G. L.C.P.G. P.A.G. S.E.H. M.L. F.M. J.M. H.N. M.O. K.P. S.P. B.P. F.S.-S. C.S. C.T. E.T. A.T.V.-v.S. F.R.Z. H.S. R.K.E. E.E.E. N.L.V. Y.W. J.L.G. R.J.W. J.R. G.W.E.S.; Supervision: M.C.H. G.W.E.S.; Validation: P.J.v.d.S. G.W.E.S.; Visualization: P.J.v.d.S. G.W.E.S.; Writing-original draft: P.J.v.d.S. M.C.H. G.W.E.S.; Writing-review and editing: P.J.v.d.S. M.J. C.A. T.A.-B. K.G. C.D. M.F. T.W. E.C.K.-N. K.P.A. P.A. C.P,B. M.A. A.Ba. M.v.d.B. S.B. T.B. A.By. M.C. C.C. K.C. A.M.C.-G. J.C.D. K.E.M.D. D.D. S.F. E.H.G. S.G. L.C.P.G. P.A.G. S.E.H. M.L. F.M. J.M. H.N. M.O. K.P. S.P. B.P. F.S.-S. C.S. C.T. E.T. A.T.V.-v.S. F.R.Z. H.S. R.K.E. E.E.E. N.L.V. Y.W. J.L.G. R.J.W. J.R. M.C.H. G.W.E.S. The Institutional Review Board of Leiden University Medical Center, Leiden, The Netherlands provided approval waivers for using de-identified data and publishing aggregated data (no: G18.098 and G21.129) without obtaining specific informed consent. Clinical data was de-identified by allocating patient numbers. Where possible, informed consent was obtained by the referring clinician. Publisher Copyright: {\textcopyright} 2022 American College of Medical Genetics and Genomics",

year = "2022",

month = aug,

doi = "10.1016/j.gim.2022.04.010",

language = "English",

volume = "24",

pages = "1753--1760",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Nature Publishing Group",

number = "8",

}

van der Sluijs, PJ, Joosten, M, Alby, C, Attié-Bitach, T, Gilmore, K, Dubourg, C, Fradin, M, Wang, T, Kurtz-Nelson, EC, Ahlers, KP, Arts, P, Barnett, CP, Ashfaq, M, Baban, A, van den Born, M, Borrie, S, Busa, T, Byrne, A, Carriero, M, Cesario, C, Chong, K, Cueto-González, AM, Dempsey, JC, Diderich, KEM, Doherty, D, Farholt, S, Gerkes, EH, Gorokhova, S, Govaerts, LCP, Gregersen, PA, Hickey, SE, Lefebvre, M, Mari, F, Martinovic, J, Northrup, H, O'Leary, M, Parbhoo, K, Patrier, S, Popp, B, Santos-Simarro, F, Stoltenburg, C, Thauvin-Robinet, C, Thompson, E, Vulto-van Silfhout, AT, Zahir, FR, Scott, HS, Earl, RK, Eichler, EE, Vora, NL, Wilnai, Y, Giordano, JL, Wapner, RJ, Rosenfeld, JA, Haak, MC & Santen, GWE 2022, 'Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort', Genetics in Medicine, vol. 24, no. 8, pp. 1753-1760. https://doi.org/10.1016/j.gim.2022.04.010

TY - JOUR

T1 - Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort

AU - van der Sluijs, Pleuntje J.

AU - Joosten, Marieke

AU - Alby, Caroline

AU - Attié-Bitach, Tania

AU - Gilmore, Kelly

AU - Dubourg, Christele

AU - Fradin, Mélanie

AU - Wang, Tianyun

AU - Kurtz-Nelson, Evangeline C.

AU - Ahlers, Kaitlyn P.

AU - Arts, Peer

AU - Barnett, Christopher P.

AU - Ashfaq, Myla

AU - Baban, Anwar

AU - van den Born, Myrthe

AU - Borrie, Sarah

AU - Busa, Tiffany

AU - Byrne, Alicia

AU - Carriero, Miriam

AU - Cesario, Claudia

AU - Chong, Karen

AU - Cueto-González, Anna Maria

AU - Dempsey, Jennifer C.

AU - Diderich, Karin E.M.

AU - Doherty, Dan

AU - Farholt, Stense

AU - Gerkes, Erica H.

AU - Gorokhova, Svetlana

AU - Govaerts, Lutgarde C.P.

AU - Gregersen, Pernille A.

AU - Hickey, Scott E.

AU - Lefebvre, Mathilde

AU - Mari, Francesca

AU - Martinovic, Jelena

AU - Northrup, Hope

AU - O'Leary, Melanie

AU - Parbhoo, Kareesma

AU - Patrier, Sophie

AU - Popp, Bernt

AU - Santos-Simarro, Fernando

AU - Stoltenburg, Corinna

AU - Thauvin-Robinet, Christel

AU - Thompson, Elisabeth

AU - Vulto-van Silfhout, Anneke T.

AU - Zahir, Farah R.

AU - Scott, Hamish S.

AU - Earl, Rachel K.

AU - Eichler, Evan E.

AU - Vora, Neeta L.

AU - Wilnai, Yael

AU - Giordano, Jessica L.

AU - Wapner, Ronald J.

AU - Rosenfeld, Jill A.

AU - Haak, Monique C.

AU - Santen, Gijs W.E.

N1 - Funding Information: Sequencing and analysis of cases 5 and 18 was funded by the National Institute of Child Human Development (Grant Nos. K23 HD088742 and R01 HD105868 [to N.L.V.]). Funding Information: This work was supported, in part, by grants from the National Institutes of Health (Grant No. R01 MH101221 [to E.E.E.]). E.E.E. is an investigator of the Howard Hughes Medical Institute. Funding Information: Sequencing and analysis for individual 30 was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute , the National Eye Institute , and the National Heart, Lung, and Blood Institute (Grant Nos. UM1 HG008900 and R01 HG009141 ). Funding Information: We would like to thank Ileana Minguel for her assistance in the collection of patient data and Aude Tessier and Anne-Claire Brehin for referring cases and conducting genetic analysis. This work was supported, in part, by grants from the National Institutes of Health (Grant No. R01 MH101221 [to E.E.E.]). E.E.E. is an investigator of the Howard Hughes Medical Institute. Sequencing and analysis for individual 30 was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute (Grant Nos. UM1 HG008900 and R01 HG009141). Sequencing and analysis of cases 5 and 18 was funded by the National Institute of Child Human Development (Grant Nos. K23 HD088742 and R01 HD105868 [to N.L.V.]). Conceptualization: P.J.v.d.S. G.W.E.S.; Data Curation: P.J.v.d.S. G.W.E.S.; Formal Analysis: P.J.v.d.S. G.W.E.S.; Funding Acquisition: M.O. E.E.E. N.L.V. G.W.E.S.; Investigation: P.J.v.d.S. G.W.E.S.; Methodology: P.J.v.d.S. G.W.E.S.; Project Administration: P.J.v.d.S.; Resources: P.J.v.d.S. M.J. C.A. T.A.-B. K.G. C.D. M.F. T.W. E.C.K.-N. K.P.A. P.A. C.P.B. M.A. A.Ba. M.v.d.B. S.B. T.B. A.By. M.C. C.C. K.C. A.M.C.-G. J.C.D. K.E.M.D. D.D. S.F. E.H.G. S.G. L.C.P.G. P.A.G. S.E.H. M.L. F.M. J.M. H.N. M.O. K.P. S.P. B.P. F.S.-S. C.S. C.T. E.T. A.T.V.-v.S. F.R.Z. H.S. R.K.E. E.E.E. N.L.V. Y.W. J.L.G. R.J.W. J.R. G.W.E.S.; Supervision: M.C.H. G.W.E.S.; Validation: P.J.v.d.S. G.W.E.S.; Visualization: P.J.v.d.S. G.W.E.S.; Writing-original draft: P.J.v.d.S. M.C.H. G.W.E.S.; Writing-review and editing: P.J.v.d.S. M.J. C.A. T.A.-B. K.G. C.D. M.F. T.W. E.C.K.-N. K.P.A. P.A. C.P,B. M.A. A.Ba. M.v.d.B. S.B. T.B. A.By. M.C. C.C. K.C. A.M.C.-G. J.C.D. K.E.M.D. D.D. S.F. E.H.G. S.G. L.C.P.G. P.A.G. S.E.H. M.L. F.M. J.M. H.N. M.O. K.P. S.P. B.P. F.S.-S. C.S. C.T. E.T. A.T.V.-v.S. F.R.Z. H.S. R.K.E. E.E.E. N.L.V. Y.W. J.L.G. R.J.W. J.R. M.C.H. G.W.E.S. The Institutional Review Board of Leiden University Medical Center, Leiden, The Netherlands provided approval waivers for using de-identified data and publishing aggregated data (no: G18.098 and G21.129) without obtaining specific informed consent. Clinical data was de-identified by allocating patient numbers. Where possible, informed consent was obtained by the referring clinician. Publisher Copyright: © 2022 American College of Medical Genetics and Genomics

PY - 2022/8

Y1 - 2022/8

N2 - Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes.Methods: Clinical data was collected through an extensive web-based survey.Results: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%).Conclusion: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.

AB - Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes.Methods: Clinical data was collected through an extensive web-based survey.Results: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%).Conclusion: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.

KW - ARID1A

KW - ARID1B BAFopathy

KW - BAF-complex

KW - Fetal

KW - SMARCA4

KW - SMARCB1

U2 - 10.1016/j.gim.2022.04.010

DO - 10.1016/j.gim.2022.04.010

M3 - Article

C2 - 35579625

AN - SCOPUS:85130377668

SN - 1098-3600

VL - 24

SP - 1753

EP - 1760

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 8

ER -