Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Phenotypes and genotypes in individuals with SMC1A variants

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Safety of switching to Migalastat from enzyme replacement therapy in Fabry disease: Experience from the Phase 3 ATTRACT study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. First reported adult patient with TARP syndrome: A case report

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Ocular albinism with infertility and late-onset sensorineural hearing loss

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Stakeholders in psychiatry and their attitudes toward receiving pertinent and incident findings in genomic research

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Patterns of sedentary time and ambulatory physical activity in a Danish population of girls and women with Rett syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Development, behaviour and autism in individuals with SMC1A variants

    Research output: Contribution to journalJournal articleResearchpeer-review

  • 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
  • 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
View graph of relations

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
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number8
Pages (from-to)2108-2125
Number of pages18
ISSN1552-4825
DOIs
Publication statusPublished - Aug 2017

    Research areas

  • Adolescent, Adult, Cell Cycle Proteins, Child, Child, Preschool, Chromosomal Proteins, Non-Histone, De Lange Syndrome, Exome, Humans, Infant, Infant, Newborn, Male, Middle Aged, Netherlands, Proteins, Rett Syndrome, Spasms, Infantile, Young Adult, Journal Article

ID: 52169851