title: Homozygous splice site mutations in PKP1 result in loss of epidermal plakophilin 1 expression and underlie ectodermal dysplasia/skin fragility syndrome in two consanguineous families.
abstract: During the last years, a growing number of inherited skin disorders have been recognized to be caused by abnormal function of desmosomal proteins. In the present study, we describe the first female individuals affected with the ectodermal dysplasia/skin fragility syndrome (MIM604536), a rare autosomal recessive disease due to mutations in the PKP1 gene encoding plakophilin 1, a critical component of desmosomal plaque. One patient was shown to carry a homozygous splice site mutation in intron 4. The second patient displayed a homozygous recurrent mutation affecting the acceptor splice site of intron 1. Both mutations were associated with intraepidermal separation, widening of intercellular spaces, and abnormal desmosome ultrastructure, and were found to result in the absence of immunoreactive plakophilin 1 in the epidermis of the affected individuals. These two cases emphasize the role of molecular genetics in the assessment of congenital blistering in newborns and illustrate the importance of proper desmosomal activity for normal epidermis development and function.
authors.affiliation: Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel. e_sprecher@rambam.health.gov.il
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.forename: Vered
authors.initials: V
authors.lastname: Molho-Pessach
authors.forename: Arieh
authors.initials: A
authors.lastname: Ingber
authors.forename: Efraim
authors.initials: E
authors.lastname: Sagi
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D009154:Mutation; D051191:Plakophilins; D011506:Proteins / Q000235:genetics*; D012326:RNA Splicing; D013577:Syndrome
chemical_list: C495335:PKP1 protein, human; D051191:Plakophilins; D011506:Proteins