title: A novel splice-site mutation in the AAGAB gene segregates with hereditary punctate palmoplantar keratoderma and congenital dysplasia of the hip in a large family.
abstract: BACKGROUND
  Palmoplantar keratoderma punctata (PPKP) is a heterogeneous group of disorders characterized by hyperkeratotic papules occurring over the palms and soles during adolescence. PPKP type 1, also known as PPKP Buschke-Fischer-Brauer type, was recently found to result from mutations in the AAGAB gene, encoding the p34 protein. PPKP type 1 is usually not associated with extracutaneous features.
  
  
  OBJECTIVE
  To investigate a large family in which PPKP1 was present in association with congenital dysplasia of the hip (CDH).
  
  
  METHODS
  A combination of direct sequencing of candidate genes and reverse-transcription PCR was used to identify the molecular basis underlying the clinical features displayed by the patients.
  
  
  RESULTS
  Direct sequencing showed a novel intronic mutation in AAGAB, which was found to cosegregate with PPKP and CDH throughout the family. The mutation was found to result in aberrant RNA splicing, leading to exon 4 skipping.
  
  
  CONCLUSIONS
  This observation suggests either the existence of a CDH-associated gene in the vicinity of AAGAB, or a hitherto unrecognized role for p34 during skeletal development.
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Eytan
authors.forename: O
authors.initials: O
authors.lastname: Sarig
authors.forename: S
authors.initials: S
authors.lastname: Israeli
authors.forename: B
authors.initials: B
authors.lastname: Mevorah
authors.forename: L
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: E
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006618:Hip Dislocation, Congenital / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D009154:Mutation; D022821:RNA Splice Sites / Q000235:genetics*
chemical_list: C579464:AAGAB protein, human; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D022821:RNA Splice Sites