The sound of silence: Autosomal recessive congenital ichthyosis caused by a synonymous mutation in ABCA12

Tomer Goldsmith, Dana Fuchs-Telem, Shirli Israeli, Ofer Sarig, Gilly Padalon-Brauch, Reuven Bergman, Margarita Indelman, Eli Sprecher*, Janna Nousbeck

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Autosomal recessive congenital ichthyosis refers to a heterogeneous group of cornification disorders of major impact on patients' life. The disease has been linked so far to mutations in 8 distinct genes. We report a consanguineous family of Arab Muslim origin with several members displaying a severe form of congenital ichthyosiform erythroderma. Using a panel of polymorphic microsatellite markers, we identified a region of homozygosity shared by all patients on 2q34, in a region harbouring the ABCA12 gene. Direct sequencing of genomic DNA derived from a patient failed to reveal any obviously pathogenic change in the coding sequence of this gene. In contrast, cDNA sequence analysis revealed the existence of a 163-bp-long deletion in exon 24, thus pointing to a splicing defect. Careful reanalysis of the genomic DNA sequence revealed apart from several known single-nucleotide polymorphisms, a hitherto unreported homozygous synonymous mutation in exon 24 (c.3456G>A; p.S1152S), which was found to lead to the formation of a novel splicing acceptor site. Synonymous mutations have been shown to uncommonly cause inherited disorders in humans. Here, we present the first example of a congenital form of ichthyosis resulting from such a genetic defect.

Original languageEnglish
Pages (from-to)251-254
Number of pages4
JournalExperimental Dermatology
Issue number4
StatePublished - Apr 2013


  • ABCA12
  • Ichthyosis
  • Mutation
  • Silent
  • Splicing


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