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. (1st March 2014)

• Record Type: Journal Article
• Authors: Eytan, O.; Sarig, O.; Israeli, S.; Mevorah, B.; Basel‐Vanagaite, L.; Sprecher, E.
• Is Part Of: Clinical and experimental dermatology. Volume 39:Number 2(2014)
• Page Start: 182
• Page End: 186
• Publication Date: 2014-03-01
• Subjects: Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/ced.12213
• Languages: English
• ISSNs: 0307-6938

Abstract

Summary: 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. Aim: 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.