ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
23064416 Pohler et al 2012: 18 families with autosomal dominant punctate palmoplantar keratoderma were shown to have loss of function mutations (variety of nonsense, frameshift and splicing mutations) in AAGAB. The skin findings were variable, with both mild and severe manifestations and onset in the first or second decade of life. Authors of this paper state that anecdotal association of AAGAB mutations with neoplasia has not been proven and may be coincidental.
23000146 Giel et al 2012: 2 novel nonsense mutations described in 3 independent pedigrees segregating autosomal dominant punctate palmoplantar keratoderma. Both intra- and inter-familial phenotypic heterogeneity was described.

Haploinsufficiency phenotype comments:

Punctate palmoplantar keratoderma (PPKP) type I (PPKP1), also called keratosis punctate palmoplantaris type Buschke-Fischer-Brauer, is a rare hereditary skin disease of the palms and soles and is characterized by multiple hyperkeratotic papules and central indentation irregularly distributed on the palms and soles. This disorder was recently found to be associated with haploinsufficiency of AAGAB.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No focal duplications were found at the time of this review.