Open AccessA novel homozygous nonsense mutation in CAST associated with PLACK syndrome
Author(s) -
Şehime Gülsün Temel,
Bedri Karakas,
Ümmühan Şeker,
Burcu Türkgenç,
Özge Zorlu,
Hayriye Sarıcaoğlu,
Çağrı Oğur,
Özgür Kütük,
David P. Kelsell,
Mustafa Cengiz Yakıcıer
Publication year - 2019
Publication title -
cell and tissue research/cell and tissue research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.64
H-Index - 137
eISSN - 1432-0878
pISSN - 0302-766X
DOI - 10.1007/s00441-019-03077-9
Subject(s) - calpastatin , sanger sequencing , exome sequencing , nonsense mutation , genetics , biology , microbiology and biotechnology , gene , genomic dna , missense mutation , medicine , mutation , calpain , biochemistry , enzyme
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.