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

作者：Eytan O; Sarig O; Israeli S; Mevorah B; Basel Vanagaite L; Sprecher E^*

来源：Clinical and Experimental Dermatology, 2014, 39(2): 182-186.

DOI：10.1111/ced.12213

BackgroundPalmoplantar 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.
AimTo investigate a large family in which PPKP1 was present in association with congenital dysplasia of the hip (CDH).
MethodsA 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.
ResultsDirect 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.
ConclusionsThis 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.

• 出版日期2014-3