Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Delineation of phenotypes and genotypes related to cohesin structural protein RAD21

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Deciphering the premature mortality in PIGA-CDG - An untold story

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A)

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Lianne C Krab
  • Iñigo Marcos-Alcalde
  • Melissa Assaf
  • Meena Balasubramanian
  • Janne Bayer Andersen
  • Anne-Marie Bisgaard
  • David R Fitzpatrick
  • Sanna Gudmundsson
  • Sylvia A Huisman
  • Tugba Kalayci
  • Saskia M Maas
  • Francisco Martinez
  • Shane McKee
  • Leonie A Menke
  • Paul A Mulder
  • Oliver D Murch
  • Michael Parker
  • Juan Pie
  • Feliciano J Ramos
  • Claudine Rieubland
  • Jill A Rosenfeld Mokry
  • Emanuela Scarano
  • Marwan Shinawi
  • Paulino Gómez-Puertas
  • Raoul C Hennekam
  • Zeynep Tümer
Vis graf over relationer

RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype-phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype-phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.

OriginalsprogEngelsk
TidsskriftHuman Genetics
Vol/bind139
Udgave nummer5
Sider (fra-til)575-592
Antal sider18
ISSN0340-6717
DOI
StatusUdgivet - maj 2020

ID: 59748458