Genetics of Inherited Ichthyoses and Related Diseases
Judith Fischer, Emmanuelle Bourrat
Inherited ichthyoses are classified as Mendelian disorders of cornification (MEDOC), which are defined on the basis of clinical and genetic features and are mainly divided into non-syndromic and syndromic ichthyoses. Numerous genes, which encode for corresponding proteins, are involved in the normal differentiation of keratinocytes (cornification) and participate in the formation of a functional epidermal barrier. To date, mutations in more than 50 genes are known to result in various types of ichthyoses. Thanks to modern genetic diagnostic methods based on targeted next generation sequencing (NGS), approximately 80–90% of cases can be resolved at present. Further sequencing methods covering the whole exome (WES) or whole genome (WGS) will obviously elucidate another portion of the remaining unknown ichthyoses in the future.
Knowledge of the molecular genetic causes and mechanisms of hereditary ichthyoses has increased hugely since the 1990s due to the ubiquitous application of modern sequencing technologies. It is important for doctors and scientists that this new knowledge is clinically and genetically correctly classified, in order to make diagnosis and differential diagnosis easier. This article provides an overview of the genetic background and clinical features of ichthyoses and related cornification disorders.