A novel homozygous nonsense mutation in CAST associated with PLACK syndrome
A novel homozygous nonsense mutation in CAST associated with PLACK syndrome
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Tarih
2019-01-01
Yazarlar
Temel, Sehime Gulsun
Karakas, B.
Seker, U.
Turkgenc, B.
Zorlu, O.
Saricaoglu, H.
Ogur, C.
Kutuk, O.
Kelsell, D. P.
Yakicier, M. C.
Süreli Yayın başlığı
Süreli Yayın ISSN
Cilt Başlığı
Yayınevi
SPRINGER
Dergi Adı
CELL AND TISSUE RESEARCH
Özet
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.
Açıklama
Anahtar kelimeler
Peeling skin syndrome, PLACK syndrome, Whole exome sequencing, CAST gene, Calpastatin