A novel homozygous nonsense mutation in CAST associated with PLACK syndrome.

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.

journal_name

Cell Tissue Res

journal_title

Cell and tissue research

authors

Temel ŞG,Karakaş B,Şeker Ü,Turkgenç B,Zorlu Ö,Sarıcaoğlu H,Oğur Ç,Kütük Ö,Kelsell DP,Yakıcıer MC

doi

10.1007/s00441-019-03077-9

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

267-277

issue

2

eissn

0302-766X

issn

1432-0878

pii

10.1007/s00441-019-03077-9

journal_volume

378

pub_type

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