A novel RAD21 variant associated with intrafamilial phenotypic variation in Cornelia de Lange syndrome

TY - JOUR

T1 - A novel RAD21 variant associated with intrafamilial phenotypic variation in Cornelia de Lange syndrome

AU - Boyle, M I

AU - Jespersgaard, C

AU - Nazaryan, L

AU - Bisgaard, A-M

AU - Tümer, Z

N1 - © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - Adult

KW - Codon, Nonsense/genetics

KW - De Lange Syndrome/diagnosis

KW - Female

KW - Humans

KW - Nuclear Proteins/genetics

KW - Penetrance

KW - Phosphoproteins/genetics

KW - Polymorphism, Single Nucleotide

KW - Sequence Deletion/genetics

U2 - 10.1111/cge.12863

DO - 10.1111/cge.12863

M3 - Letter

C2 - 27882533

SN - 0009-9163

VL - 91

SP - 647

EP - 649

JO - Clinical Genetics

JF - Clinical Genetics

IS - 4

ER -