A Cryptic CBFB Deletion-Inversion Expands the Mutational Spectrum of Variants Associated With Cleidocranial Dysplasia.

ABSTRACT: CBFB encodes the core-binding factor β subunit, a small protein which heterodimerises with RUNX1-3 and activates transcription of genes important in bone development. Recently, five families with cleidocranial dysplasia (CCD) were identified harbouring presumed loss of function variants in CBFB. Prompted by a multidisciplinary team review of an affected mother and daughter from the 100 000 Genomes Project with genetically unsolved CCD, we inspected read alignments and identified a deletion-inversion-deletion that removes the first two exons of CBFB. This cryptic variant comprised interlinked deletions of 1310 bp and 1935 bp and had remained undetected by both array-CGH and the Canvas algorithm. The rearrangement was likely mediated by a palindromic AluSx repeat < 1 kb from the transcriptio

SUBMITTER: Pagnamenta AT 

PROVIDER: S-EPMC12136864 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature