A novel homozygous nonsense mutation in <i>CAST</i> associated with PLACK syndrome

TEMEL Ş. G., Karakas B., Seker Ü., Turkgenc B., Zorlu O., Saricaoglu H., ...Daha Fazla

CELL AND TISSUE RESEARCH, sa.2, ss.267-277, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1007/s00441-019-03077-9
  • Dergi Adı: CELL AND TISSUE RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.267-277
  • Anahtar Kelimeler: Peeling skin syndrome, PLACK syndrome, Whole exome sequencing, CAST gene, Calpastatin, PEELING SKIN SYNDROME, MISSENSE MUTATION, CALPASTATIN, LEUKONYCHIA, CALPAINS, SURVIVAL, REVEALS, PROMOTE, DEATH, GENE
  • Bursa Uludağ Üniversitesi Adresli: Evet

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.