title: Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept.
abstract: Hailey-Hailey disease (HHD) is an autosomal dominant trait characterized by erythematous and oozing skin lesions preponderantly involving the body folds. In the present unusual case, however, unilateral segmental areas along the lines of Blaschko showing a rather severe involvement were superimposed on the ordinary symmetrical phenotype. Based on this observation and similar forms of mosaicism as reported in other autosomal dominant skin disorders, we postulated that in such cases, 2 different types of segmental involvement can be distinguished. Accordingly, the linear lesions as noted in the present case would exemplify type 2 segmental HHD. In the heterozygous embryo, loss of heterozygosity occurring at an early developmental stage would have given rise to pronounced linear lesions reflecting homozygosity or hemizygosity for the mutation. By analyzing DNA and RNA derived from blood and skin samples as well as keratinocytes of the index patient with various molecular techniques including RT-PCR, real-time PCR, and microsatellite analysis, we found a consistent loss of the paternal wild-type allele in more severely affected segmental skin regions, confirming this hypothesis for the first time, to our knowledge, at the molecular and cellular level.
authors.affiliation: Department of Dermatology and Allergology, University Clinic of the Rheinisch Westfäkusche Technische Hochschule Aachen, Aachen, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Poblete-Gutiérrez
authors.forename: Tonio
authors.initials: T
authors.lastname: Wiederholt
authors.forename: Arne
authors.initials: A
authors.lastname: König
authors.forename: Frank K
authors.initials: FK
authors.lastname: Jugert
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Marquardt
authors.forename: Albert
authors.initials: A
authors.lastname: Rübben
authors.forename: Hans F
authors.initials: HF
authors.lastname: Merk
authors.forename: Rudolf
authors.initials: R
authors.lastname: Happle
authors.forename: Jorge
authors.initials: J
authors.lastname: Frank
mesh_terms: D000483:Alleles; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D002478:Cells, Cultured; D002893:Chromosomes, Human, Pair 3; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D005799:Genes, Dominant; D005819:Genetic Markers; D018095:Germ-Line Mutation; D006239:Haplotypes; D020180:Heteroduplex Analysis; D006579:Heterozygote; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009030:Mosaicism; D010375:Pedigree; D016506:Pemphigus, Benign Familial / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D012313:RNA / Q000097:blood / Q000235:genetics; D012867:Skin / Q000737:chemistry / Q000166:cytology
chemical_list: D005819:Genetic Markers; D012313:RNA; D004247:DNA; C403624:ATP2C1 protein, human; D000252:Calcium-Transporting ATPases