A Patient With Plack Syndrome With a Novel Splicing Mutation in Cast: The Evidence for a Loss-Of-Function Mechanism Through Mis-Splicing Publisher Pubmed



Mamivand A¹ ; Zekri A^{2, 3} ; Maghrouni A¹ ; Bayat S¹ ; Mirzaei E³ ; Golroodbari FJ³ ; Mousavi SM³ ; Behrangi E⁴ ; Tabrizi M¹
Source: Clinical and Experimental Dermatology Published:2023

Abstract

PLACK syndrome is a relatively recently defined generalized peeling skin syndrome that has been reported with major skin manifestations and sometimes atypical features. We report the case of a 5-year-old boy with PLACK manifestations. 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 this patient’s phenotype. This study extends our understanding of the various phenotypic and genotypic features of PLACK syndrome. © The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved.