title: Eight Novel Mutations Confirm the Role of AAGAB in Punctate Palmoplantar Keratoderma Type 1 (Buschke-Fischer-Brauer) and Show Broad Phenotypic Variability.
abstract: Punctate palmoplantar keratoderma (PPKP1; Buschke-Fischer-Brauer) is a rare autosomal dominant inherited skin disease characterized by multiple hyperkeratotic papules involving the palms and soles. Mutations have been found at 2 loci, on chromosomes 15q22-15q24 and 8q24.13-8q24.21. We recently identified mutations in 3 families, in the AAGAB gene on 15q, which encodes the alpha- and gamma-adaptin-binding protein p34. The current study examined 14 additional families, comprising a total of 26 affected individuals and identified 8 novel mutations in 9 families. In one family a mutation that was present only in the affected individuals was found, and in 4 other families, previously reported mutations were found (1, 2). These results confirm the role of AAGAB in PPKP1. Our findings suggest that there is no correlation with age, but with mechanical factors. No additional obvious genotype-phenotype correlation was observed, even when comparing different types of mutations. Rather, identical genotypes presented a very broad interfamilial and intrafamilial variability of phenotypes.
authors.affiliation: Department of Dermatology, Ludwig-Maximilian University, Munich, Germany. kathrin.giehl@med.uni-muenchen.de.
authors.forename: Kathrin A
authors.initials: KA
authors.lastname: Giehl
authors.forename: Thomas
authors.initials: T
authors.lastname: Herzinger
authors.forename: Hans
authors.initials: H
authors.lastname: Wolff
authors.forename: Miklós
authors.initials: M
authors.lastname: Sárdy
authors.forename: Tanja
authors.initials: T
authors.lastname: von Braunmühl
authors.forename: Valérie
authors.initials: V
authors.lastname: Dekeuleneer
authors.forename: Yves
authors.initials: Y
authors.lastname: Sznajer
authors.forename: Dominique
authors.initials: D
authors.lastname: Tennstedt
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boes
authors.forename: Stefan
authors.initials: S
authors.lastname: Rapprich
authors.forename: Nicola
authors.initials: N
authors.lastname: Wagner
authors.forename: Regina C
authors.initials: RC
authors.lastname: Betz
authors.forename: Markus
authors.initials: M
authors.lastname: Braun-Falco
authors.forename: Tim
authors.initials: T
authors.lastname: Strom
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Gertrud N
authors.initials: GN
authors.lastname: Eckstein
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: C579464:AAGAB protein, human; D033942:Adaptor Proteins, Vesicular Transport