A novel nonsense mutation in the STS gene in a Pakistani family with X-linked recessive ichthyosis: including a very rare case of two homozygous female patients

摘要

Identification of a novel nonsense mutation in gene (A) Pedigree of the family with X-linked ichthyosis. The proband (IV:23) is noted with an arrow. ■, affected male; ●, affected female; ◻, healthy male; ○, healthy female. (B) Sequencing chromatogram showing the wild type normal control hemizygous affected male and heterozygous female carrier, with mutation position marked by an arrow. (C) Schematic representation of exon-intron structure of gene; exons are designated as boxes E (1–10). DNA and protein sequence of the exon 4 where the mutation c.287G > A (p.W96*) resides is shown expanded. Nucleotide and amino acid numbering correspond to for the cDNA and for the protein. Nucleotides were numbered using A of the ATG translation initiation codon as + 1 nucleotide of the coding sequence. (D) A ribbon diagram showing the secondary and tertiary structures of the wild type STS enzyme. Sheets are drawn in yellow, helices in red and loop regions in green. (a) showing β-sheets, α-helices and coils. The structure (b) denotes the potential truncated polypeptide (STS enzyme) due to p.W96* mutation (Swiss-Model). (E) Schematic illustration of the domain graph of the encoded protein (Uniprot identifier: ), and the genetic variants. A full-length wild type STS protein is shown, with its N-terminus and C-terminus. Novel variant identified in our study is boxed in red alongside previously reported point mutations and a splice- site variant underlying XLI phenotype in The Human Gene Mutation Database (HGMD®; )