Subject(s)
Arteries/abnormalities , Heart Septal Defects, Atrial/complications , Heart Septal Defects, Atrial/diagnostic imaging , Joint Instability/complications , Joint Instability/diagnostic imaging , Skin Diseases, Genetic/complications , Skin Diseases, Genetic/diagnostic imaging , Ultrasonography, Prenatal/methods , Vascular Malformations/complications , Vascular Malformations/diagnostic imaging , Adult , Aorta, Thoracic/abnormalities , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/embryology , Arteries/diagnostic imaging , Arteries/embryology , Arteries/surgery , Diagnosis, Differential , Female , Fetal Heart/abnormalities , Fetal Heart/diagnostic imaging , Fetal Heart/embryology , Humans , Infant , Infant, Newborn , Joint Instability/embryology , Joint Instability/surgery , Male , Pregnancy , Skin Diseases, Genetic/embryology , Skin Diseases, Genetic/surgery , Vascular Malformations/embryology , Vascular Malformations/surgerySubject(s)
Electron Transport Complex IV/genetics , Genetic Diseases, X-Linked/genetics , Microphthalmos/genetics , Skin Abnormalities/genetics , Skin Diseases, Genetic/genetics , Cytochrome-c Oxidase Deficiency/enzymology , Cytochrome-c Oxidase Deficiency/genetics , Electron Transport/genetics , Electron Transport/physiology , Electron Transport Complex IV/chemistry , Female , Genetic Diseases, X-Linked/embryology , Genetic Diseases, X-Linked/pathology , Humans , Infant, Newborn , Lyases/genetics , Male , Microphthalmos/embryology , Microphthalmos/pathology , Mutation , Protein Subunits , Skin/embryology , Skin Abnormalities/embryology , Skin Abnormalities/pathology , Skin Diseases, Genetic/embryology , Skin Diseases, Genetic/pathologySubject(s)
Chromosome Aberrations , Genes, Dominant/genetics , Haplotypes , Leiomyomatosis/genetics , Loss of Heterozygosity , Skin Diseases, Genetic/genetics , Skin Neoplasms/genetics , Alleles , Female , Humans , Leiomyomatosis/embryology , Neurofibromatosis 1/embryology , Neurofibromatosis 1/genetics , Pregnancy , Skin Diseases, Genetic/embryology , Skin Neoplasms/embryologyABSTRACT
Autosomal dominant disorders of the skin may present in a pattern following the lines of embryologic development of the ectoderm. In these cases, the surrounding skin is normal, and molecular studies have shown that the causative mutation is confined to the affected ectodermal tissue (type 1 mosaicism). Rarely, an individual shows skin lesions that follow the pattern of type 1 mosaicism, but the rest of the skin shows a milder form of the disorder (type 2 mosaicism). A new study provides the molecular basis for type 2 mosaicism.
Subject(s)
Mosaicism/classification , Mosaicism/embryology , Skin Diseases, Genetic/classification , Skin Diseases, Genetic/genetics , Skin Diseases, Genetic/pathology , Body Patterning/genetics , Calcium-Transporting ATPases/genetics , Chromosome Disorders , Ectoderm/pathology , Focal Dermal Hypoplasia/genetics , Focal Dermal Hypoplasia/pathology , Gene Dosage , Genes, Dominant , Germ-Line Mutation , Heterozygote , Humans , Keratinocytes/pathology , Models, Genetic , Mutation, Missense , Pemphigus, Benign Familial/genetics , Pemphigus, Benign Familial/pathology , Scleroderma, Localized/genetics , Scleroderma, Localized/pathology , Skin Diseases, Genetic/embryologyABSTRACT
The prevailing theory says that mosaic forms of autosomal dominant skin diseases originate from postzygotic new mutations. This theory is no longer generally valid. According to a new rule of dichotomy, we can distinguish two types of segmental manifestations. The type 1 reflects heterozygosity for a postzygotic new mutation, whereas the type 2 results from loss of the corresponding wildtype allele occurring in a heterozygous embryo and reflects either homozygosity or hemizygosity for the underlying mutation, giving rise to rather pronounced segmental lesions that are superimposed on the ordinary nonsegmental phenotype. Autosomal dominant skin diseases exemplifying the concept of type 2 segmental manifestation so far include neurofibromatosis 1, tuberous sclerosis, cutaneous leiomyomatosis, glomangiomatosis, Buschke-Ollendorff syndrome, multiple syringomas, multiple trichoepitheliomas, multiple basaloid follicular hamartomas, multiple nevoid basal cell carcinomas, Darier disease, Hailey-Hailey disease, epidermolytic hyperkeratosis of Brocq, KID syndrome, disseminated superficial actinic porokeratosis and autosomal dominant dyskeratosis congenita. A strikingly high frequency of type 2 segmental involvement has been documented in cutaneous leiomyomatosis, glomangiomatosis and disseminated superficial actinic porokeratosis. It should be noted that there is so far no molecular proof for the proposed rule of dichotomy that has been developed from clinical dermatology. According to present knowledge, however, it is very likely that molecular analysis will confirm the described concept that can explain some so far enigmatic features as observed in autosomal dominant genodermatoses.