A patient with PLACK syndrome with a novel splicing mutation in CAST: the evidence for a loss-of-function mechanism through mis-splicing

Abstract

PLACK syndrome is a relatively recently defined generalized Peeling Skin Syndrome (PSS) that has been reported with major skin manifestations and sometimes atypical features. Herein, the case of a five-year-old boy with PLACK manifestations is reported. Whole exome sequencing and subsequent Sanger sequencing identified a putative splice variant c.1209 + 2T > G in CAST (NM_001042440.5). Moreover, mRNA sequencing confirmed the abnormal alternative splicing of the CAST gene leading to the addition of one nucleotide to the correct open reading frame at the mRNA level. Segregation and expression analysis revealed that this loss-of-function via mRNA nonsense-mediated decay could be the causative pathogenic mechanism responsible for the patient’s phenotype. This study extends our understanding of the various phenotypic and genotypic features of PLACK disease.