title: A novel RAD21 variant associated with intrafamilial phenotypic variation in Cornelia de Lange syndrome - review of the literature.
abstract: In a patient with CdLS (IV.16) we identifed a novel single basepair deletion (c.704delG) in RAD21, which encodes a cohesin pathway protein. The variant is predicted to result in a premature stop codon [p.(Ser235Ilefs*19)] and hereby would have a deleterious effect. RAD21 variants have previously been described only in five cases with cohesinopathies (b). Notably, the deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study (a). The index patient can be classified as mild CdLS, but the other family members do not fulfill the diagnostic criteria of CdLS. This study together with previous reports suggests incomplete penetrance associated with RAD21 variants and these individuals may therefore be underdiagnosed.
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: M I
authors.initials: MI
authors.lastname: Boyle
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Jespersgaard
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Nazaryan
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: A-M
authors.initials: AM
authors.lastname: Bisgaard
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Z
authors.initials: Z
authors.lastname: Tümer
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense / Q000235:genetics; D004268:DNA-Binding Proteins; D003635:De Lange Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D019683:Penetrance; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C429022:RAD21 protein, human