Punctate Palmoplantar Keratoderma Type 1: A Novel AAGAB Mutation and Efficacy of Etretinate

Punctate palmoplantar keratoderma type 1 (PPKP1, OMIM#148600), also known as the Buschke-FischerBraurer type, is a rare form of palmoplantar keratoderma that is autosomal dominantly inherited (1). PPKP1 is clinically characterised by multiple punctate hyperkeratotic papules affecting the palmar and plantar skin, with considerable phenotypic variation among patients (2). These circumscribed papules gradually coalesce and increase in number with age (2). The lesions typically start to appear in early adolescence but sometimes develop later in life. In 2012, linkage analysis and whole-exome sequencing identified heterozygous null mutations within AAGAB as a cause of PPKP1 (2, 3). AAGAB encodes α and γ-adaptin binding protein p34, which is involved in clathrin-mediated vesicle transport (2). Loss-of-function mutations in AAGAB result in haploinsufficiency of p34 (2). To date, 20 AAGAB null variants have been identified in Scottish, Irish, English, German, Tunisian, Chinese Mexican and Japanese populations (2–8). Here we report a Japanese case with PPKP1 carrying a novel AAGAB null mutation.