Unknown mutations and genotype/phenotype correlations of autosomal recessive congenital ichthyosis in patients from Saudi Arabia and Pakistan

Dulce Lima Cunha, Omar Mohammed Alakloby, Robert Gruber, Naseebullah Kakar, Jamil Ahmad, Salem Alawbathani, Roswitha Plank, Katja Eckl, Birgit Krabichler, Janine Altmüller, Peter Nurnberg, Johannes Zschocke, Guntram Borck, Matthias Schmuth, Adnan S. Alabdulkareem, Kholood Abdulaziz Alnutaifi, Hans Christian Hennies

Research output: Contribution to journalArticle (journal)peer-review

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BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a genetically and phenotypically heterogeneous skin disease, associated with defects in the skin permeability barrier. Several but not all genes with underlying mutations have been identified, but a clear correlation between genetic causes and clinical picture has not been described to date. METHODS: Our study included 19 families from Saudi Arabia, Yemen, and Pakistan. All patients were born to consanguineous parents and diagnosed with ARCI. Mutations were analyzed by homozygosity mapping and direct sequencing. RESULTS: We have detected mutations in all families in five different genes: TGM1, ABCA12, CYP4F22, NIPAL4, and ALOXE3. Five likely pathogenic variants were unknown so far, a splice site and a missense variant in TGM1, a splice site variant in NIPAL4, and missense variants in ABCA12 and CYP4F22. We attributed TGM1 and ABCA12 mutations to the most severe forms of lamellar and erythematous ichthyoses, respectively, regardless of treatment. Other mutations highlighted the presence of a phenotypic spectrum in ARCI. CONCLUSION: Our results contribute to expanding the mutational spectrum of ARCI and revealed new insights into genotype/phenotype correlations. The findings are instrumental for a faster and more precise diagnosis, a better understanding of the pathophysiology, and the definition of targets for more specific therapies for ARCI.
Original languageEnglish
Pages (from-to)e539
JournalMolecular genetics & genomic medicine
Issue number3
Early online date1 Jan 2019
Publication statusPublished - 1 Mar 2019


  • ATP-Binding Cassette Transporters/genetics
  • Adolescent
  • Child
  • Cytochrome P-450 Enzyme System/genetics
  • Female
  • Genes, Recessive
  • Genotype
  • Humans
  • Ichthyosiform Erythroderma, Congenital/epidemiology
  • Lipoxygenase/genetics
  • Male
  • Mutation Rate
  • Pakistan
  • Phenotype
  • Receptors, Cell Surface/genetics
  • Saudi Arabia
  • Transglutaminases/genetics
  • Young Adult


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