Introduction
Vered Molho-Pessach and Julie V. Schaffer Genetic Basis of Cutaneous Diseases 55
Key features
Advances in molecular technology have led to elucidation of the genetic bases of many single-gene inherited and mosaic skin disorders, greatly improving our understanding of these conditions
McKusick’s Online Mendelian Inheritance in Man (OMIM) database provides easily accessible, up-to-date information on human genes and genetic diseases; each gene or phenotype entry is assigned a specific six-digit MIM number
Genotype–phenotype correlations in genodermatoses are often complex, with multiple examples of allelic heterogeneity (mutations in a single gene causing more than one disorder) and locus heterogeneity (mutations in different genes causing the same disorder)
Molecular classification of genodermatoses into categories such as keratin defects and RASopathies complements traditional morphologic classification, highlighting pathomechanisms and relationships between conditions
Certain syndromic associations actually represent contiguous gene syndromes caused by large deletions that affect two or more neighboring genes
Types 1 and 2 mosaicism in autosomal dominant disorders have been confirmed on a molecular level, and functional X-chromosome mosaicism can lead to a mosaic distribution of skin lesions in female patients heterozygous for X-linked disorders
Determining the molecular basis of monogenic skin disorders can enable the development of targeted therapies and provide insights into the pathogenesis of acquired skin diseases
Molecular research has paved the way to the goal of gene therapy for severe inherited skin disorders such as epidermolysis bullosa
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; XD, X-linked dominant; XR, X-linked recessive.