A novel homozygous nonsense mutation in CAST associated with PLACK syndrome

Cell and Tissue Research
Şehime Gülsün TemelM C Yakıcıer

Abstract

Peeling skin syndrome is a heterogeneous group of rare disorders. Peeling skin, leukonychia, acral punctate keratoses, cheilitis and knuckle pads (PLACK syndrome, OMIM616295) is a newly described form of PSS with an autosomal recessive mode of inheritance. We report a 5.5-year-old boy with features of PLACK syndrome. Additionally, he had mild cerebral atrophy and mild muscle involvements. Whole exome sequencing was performed in genomic DNA of this individual and subsequent analysis revealed a homozygous c.544G > T (p.Glu182*) nonsense mutation in the CAST gene encoding calpastatin. Sanger sequencing confirmed this variant and demonstrated that his affected aunt was also homozygous. Real-time qRT-PCR and immunoblot analysis showed reduced calpastatin expression in skin fibroblasts derived from both affected individuals compared to heterozygous family members. In vitro calpastatin activity assays also showed decreased activity in affected individuals. This study further supports a key role for calpastatin in the tight regulation of proteolytic pathways within the skin.

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Citations

Oct 4, 2020·Pediatric Dermatology·Jennifer M E Boggs, Alan D Irvine
Sep 13, 2020·Clinical and Experimental Dermatology·S O'SullivanA E Martinez
Jan 8, 2021·Clinical Genetics·Zinab A SawanMohammed Abanemai

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Methods Mentioned

BETA
exome sequencing
PCR
biopsies
transmission electron microscopy
Transmission
transgenic

Software Mentioned

GATK UnifiedGenotyper
BWA
GraphPad Prism
Illumina
FMFilter
Genome Analysis Toolkit
HGMD
ImageQuant
BEDtools
Provean

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