RT Journal Article
SR Electronic
T1 <em>CHEK2</em> is not a Li-Fraumeni syndrome gene: time to update public resources
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 1215
OP 1217
DO 10.1136/jmg-2023-109464
VO 60
IS 12
A1 Fortuno, Cristina
A1 Richardson, Marcy
A1 Pesaran, Tina
A1 Yussuf, Amal
A1 Horton, Carolyn
A1 James, Paul A
A1 Spurdle, Amanda B
YR 2023
UL http://jmg.bmj.com/content/60/12/1215.abstract
AB The gene-disease relationship for CHEK2 remains listed as ‘Li-Fraumeni syndrome 2’ in public resources such as OMIM and MONDO, despite published evidence to the contrary, causing frustration among Li-Fraumeni syndrome (LFS) clinical experts. Here, we compared personal cancer characteristics of 2095 CHEK2 and 248 TP53 pathogenic variant carriers undergoing multigene panel testing at Ambry Genetics against 15 135 individuals with no known pathogenic variant. Our results from a within-cohort logistic regression approach highlight obvious differences between clinical presentation of TP53 and CHEK2 pathogenic variant carriers, with no evidence of CHEK2 being associated with any of the TP53-related core LFS cancers. These findings emphasise the need to replace ‘Li-Fraumeni syndrome 2’ as the CHEK2-associated disease name, thereby limiting potential confusion.