A novel homozygous nonsense mutation in CAST associated with PLACK syndrome

Temel, Şehime Gülsün and Karakaş, Bahriye and Şeker, U. and Turkgenç, B. and Zorlu, O. and Sarıcaoğlu, H. and Oğur, C. and Kütük, O. and Kelsell, D. P. and Yakıcıer, M. C. (2019) A novel homozygous nonsense mutation in CAST associated with PLACK syndrome. Cell and Tissue Research, 378 (2). pp. 267-277. ISSN 0302-766X (Print) 1432-0878 (Online)

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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.
Item Type: Article
Uncontrolled Keywords: Calpastatin; CAST gene; Peeling skin syndrome; PLACK syndrome; Whole exome sequencing
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Bahriye Karakaş
Date Deposited: 25 Jul 2023 15:44
Last Modified: 25 Jul 2023 15:44
URI: https://research.sabanciuniv.edu/id/eprint/46257

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