Phenotypes and genotypes in individuals with SMC1A variants

Sylvia Huisman, Paul A. Mulder, Egbert Redeker, Ingrid Bader, Anne Marie Bisgaard, Alice Brooks, Anna Cereda, Constanza Cinca, Dinah Clark, Valerie Cormier-Daire, Matthew A. Deardorff, Karin Diderich, Mariet Elting, Anthonie van Essen, David FitzPatrick, Cristina Gervasini, Gabriele Gillessen-Kaesbach, Katta M. Girisha, Yvonne Hilhorst-Hofstee, Saskia Hopman & 28 others Denise Horn, Mala Isrie, Sandra Jansen, Cathrine Jespersgaard, Frank J. Kaiser, Maninder Kaur, Tjitske Kleefstra, Ian D. Krantz, Phillis Lakeman, Annemiek Landlust, Davor Lessel, Caroline Michot, Jo Moss, Sarah E. Noon, Chris Oliver, Ilaria Parenti, Juan Pie, Feliciano J. Ramos, Claudine Rieubland, Silvia Russo, Angelo Selicorni, Zeynep Tümer, Rieneke Vorstenbosch, Tara L. Wenger, Ingrid van Balkom, Sigrid Piening, Jolanta Wierzba, Raoul C. Hennekam

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.

Original languageEnglish
Pages (from-to)2108-2125
Number of pages18
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number8
DOIs
Publication statusPublished - 01-08-2017

Fingerprint

De Lange Syndrome
Genotype
Phenotype
Rett Syndrome
Brain Diseases
Interdisciplinary Studies
Exome
Self-Injurious Behavior
Frameshift Mutation
Nonsense Codon
Missense Mutation
Intellectual Disability
Netherlands
Genes
Epilepsy
Extremities
Growth
cohesins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Huisman, S., Mulder, P. A., Redeker, E., Bader, I., Bisgaard, A. M., Brooks, A., ... Hennekam, R. C. (2017). Phenotypes and genotypes in individuals with SMC1A variants. American Journal of Medical Genetics, Part A, 173(8), 2108-2125. https://doi.org/10.1002/ajmg.a.38279
Huisman, Sylvia ; Mulder, Paul A. ; Redeker, Egbert ; Bader, Ingrid ; Bisgaard, Anne Marie ; Brooks, Alice ; Cereda, Anna ; Cinca, Constanza ; Clark, Dinah ; Cormier-Daire, Valerie ; Deardorff, Matthew A. ; Diderich, Karin ; Elting, Mariet ; van Essen, Anthonie ; FitzPatrick, David ; Gervasini, Cristina ; Gillessen-Kaesbach, Gabriele ; Girisha, Katta M. ; Hilhorst-Hofstee, Yvonne ; Hopman, Saskia ; Horn, Denise ; Isrie, Mala ; Jansen, Sandra ; Jespersgaard, Cathrine ; Kaiser, Frank J. ; Kaur, Maninder ; Kleefstra, Tjitske ; Krantz, Ian D. ; Lakeman, Phillis ; Landlust, Annemiek ; Lessel, Davor ; Michot, Caroline ; Moss, Jo ; Noon, Sarah E. ; Oliver, Chris ; Parenti, Ilaria ; Pie, Juan ; Ramos, Feliciano J. ; Rieubland, Claudine ; Russo, Silvia ; Selicorni, Angelo ; Tümer, Zeynep ; Vorstenbosch, Rieneke ; Wenger, Tara L. ; van Balkom, Ingrid ; Piening, Sigrid ; Wierzba, Jolanta ; Hennekam, Raoul C. / Phenotypes and genotypes in individuals with SMC1A variants. In: American Journal of Medical Genetics, Part A. 2017 ; Vol. 173, No. 8. pp. 2108-2125.
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abstract = "SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.",
author = "Sylvia Huisman and Mulder, {Paul A.} and Egbert Redeker and Ingrid Bader and Bisgaard, {Anne Marie} and Alice Brooks and Anna Cereda and Constanza Cinca and Dinah Clark and Valerie Cormier-Daire and Deardorff, {Matthew A.} and Karin Diderich and Mariet Elting and {van Essen}, Anthonie and David FitzPatrick and Cristina Gervasini and Gabriele Gillessen-Kaesbach and Girisha, {Katta M.} and Yvonne Hilhorst-Hofstee and Saskia Hopman and Denise Horn and Mala Isrie and Sandra Jansen and Cathrine Jespersgaard and Kaiser, {Frank J.} and Maninder Kaur and Tjitske Kleefstra and Krantz, {Ian D.} and Phillis Lakeman and Annemiek Landlust and Davor Lessel and Caroline Michot and Jo Moss and Noon, {Sarah E.} and Chris Oliver and Ilaria Parenti and Juan Pie and Ramos, {Feliciano J.} and Claudine Rieubland and Silvia Russo and Angelo Selicorni and Zeynep T{\"u}mer and Rieneke Vorstenbosch and Wenger, {Tara L.} and {van Balkom}, Ingrid and Sigrid Piening and Jolanta Wierzba and Hennekam, {Raoul C.}",
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Huisman, S, Mulder, PA, Redeker, E, Bader, I, Bisgaard, AM, Brooks, A, Cereda, A, Cinca, C, Clark, D, Cormier-Daire, V, Deardorff, MA, Diderich, K, Elting, M, van Essen, A, FitzPatrick, D, Gervasini, C, Gillessen-Kaesbach, G, Girisha, KM, Hilhorst-Hofstee, Y, Hopman, S, Horn, D, Isrie, M, Jansen, S, Jespersgaard, C, Kaiser, FJ, Kaur, M, Kleefstra, T, Krantz, ID, Lakeman, P, Landlust, A, Lessel, D, Michot, C, Moss, J, Noon, SE, Oliver, C, Parenti, I, Pie, J, Ramos, FJ, Rieubland, C, Russo, S, Selicorni, A, Tümer, Z, Vorstenbosch, R, Wenger, TL, van Balkom, I, Piening, S, Wierzba, J & Hennekam, RC 2017, 'Phenotypes and genotypes in individuals with SMC1A variants', American Journal of Medical Genetics, Part A, vol. 173, no. 8, pp. 2108-2125. https://doi.org/10.1002/ajmg.a.38279

Phenotypes and genotypes in individuals with SMC1A variants. / Huisman, Sylvia; Mulder, Paul A.; Redeker, Egbert; Bader, Ingrid; Bisgaard, Anne Marie; Brooks, Alice; Cereda, Anna; Cinca, Constanza; Clark, Dinah; Cormier-Daire, Valerie; Deardorff, Matthew A.; Diderich, Karin; Elting, Mariet; van Essen, Anthonie; FitzPatrick, David; Gervasini, Cristina; Gillessen-Kaesbach, Gabriele; Girisha, Katta M.; Hilhorst-Hofstee, Yvonne; Hopman, Saskia; Horn, Denise; Isrie, Mala; Jansen, Sandra; Jespersgaard, Cathrine; Kaiser, Frank J.; Kaur, Maninder; Kleefstra, Tjitske; Krantz, Ian D.; Lakeman, Phillis; Landlust, Annemiek; Lessel, Davor; Michot, Caroline; Moss, Jo; Noon, Sarah E.; Oliver, Chris; Parenti, Ilaria; Pie, Juan; Ramos, Feliciano J.; Rieubland, Claudine; Russo, Silvia; Selicorni, Angelo; Tümer, Zeynep; Vorstenbosch, Rieneke; Wenger, Tara L.; van Balkom, Ingrid; Piening, Sigrid; Wierzba, Jolanta; Hennekam, Raoul C.

In: American Journal of Medical Genetics, Part A, Vol. 173, No. 8, 01.08.2017, p. 2108-2125.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phenotypes and genotypes in individuals with SMC1A variants

AU - Huisman, Sylvia

AU - Mulder, Paul A.

AU - Redeker, Egbert

AU - Bader, Ingrid

AU - Bisgaard, Anne Marie

AU - Brooks, Alice

AU - Cereda, Anna

AU - Cinca, Constanza

AU - Clark, Dinah

AU - Cormier-Daire, Valerie

AU - Deardorff, Matthew A.

AU - Diderich, Karin

AU - Elting, Mariet

AU - van Essen, Anthonie

AU - FitzPatrick, David

AU - Gervasini, Cristina

AU - Gillessen-Kaesbach, Gabriele

AU - Girisha, Katta M.

AU - Hilhorst-Hofstee, Yvonne

AU - Hopman, Saskia

AU - Horn, Denise

AU - Isrie, Mala

AU - Jansen, Sandra

AU - Jespersgaard, Cathrine

AU - Kaiser, Frank J.

AU - Kaur, Maninder

AU - Kleefstra, Tjitske

AU - Krantz, Ian D.

AU - Lakeman, Phillis

AU - Landlust, Annemiek

AU - Lessel, Davor

AU - Michot, Caroline

AU - Moss, Jo

AU - Noon, Sarah E.

AU - Oliver, Chris

AU - Parenti, Ilaria

AU - Pie, Juan

AU - Ramos, Feliciano J.

AU - Rieubland, Claudine

AU - Russo, Silvia

AU - Selicorni, Angelo

AU - Tümer, Zeynep

AU - Vorstenbosch, Rieneke

AU - Wenger, Tara L.

AU - van Balkom, Ingrid

AU - Piening, Sigrid

AU - Wierzba, Jolanta

AU - Hennekam, Raoul C.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.

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Huisman S, Mulder PA, Redeker E, Bader I, Bisgaard AM, Brooks A et al. Phenotypes and genotypes in individuals with SMC1A variants. American Journal of Medical Genetics, Part A. 2017 Aug 1;173(8):2108-2125. https://doi.org/10.1002/ajmg.a.38279