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

Autor: Temel ŞG; Faculty of Medicine, Department of Medical Genetics, University of Uludag, Bursa, Turkey. sehimegtemel@hotmail.com.; Faculty of Medicine, Department of Histology & Embryology, University of Uludag, Bursa, Turkey. sehimegtemel@hotmail.com., Karakaş B; Molecular Biology, Genetics and Bioengineering Program, Sabancı University, Istanbul, Turkey., Şeker Ü; Faculty of Medicine, Department of Dermatology, University of Uludag, Bursa, Turkey., Turkgenç B; Acıbadem Genetic Diagnosis Center, University of Acıbadem, Istanbul, Turkey., Zorlu Ö; Faculty of Medicine, Department of Dermatology, University of Uludag, Bursa, Turkey., Sarıcaoğlu H; Faculty of Medicine, Department of Dermatology, University of Uludag, Bursa, Turkey., Oğur Ç; Bahçeci Genetic Diagnosis Center, Altunizade, Istanbul, Turkey., Kütük Ö; Faculty of Medicine, Department of Medical Genetics, Baskent University, Adana, Turkey., Kelsell DP; Centre for Cell Biology and Cutaneous Research, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK., Yakıcıer MC; Faculty of Arts and Sciences, Department of Molecular Biology and Genetics, University of Acibadem, Istanbul, Turkey.
Jazyk: angličtina
Zdroj: Cell and tissue research [Cell Tissue Res] 2019 Nov; Vol. 378 (2), pp. 267-277. Date of Electronic Publication: 2019 Aug 07.
DOI: 10.1007/s00441-019-03077-9
Abstrakt: 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.
Databáze: MEDLINE
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