AAGAB-pEDD (palmoplantar Epidermal Differentiation Disorder)

Commonly referred to as “Type 1 Punctate Palmar Plantar Keratoderma”

Facts

• What does AAGAB stand for? Alpha and gamma adaptin binding protein 34¹
• What does the AAGAB gene do? Participates in protein sorting & endocytosis¹
• What happens when AAGAB becomes mutated? Dysfunctional endocytic recycling of EGFR proteins¹
• Clinical significance of mutation? Cellular hyperproliferation & hyperkeratotic lesions¹

About Type 1 Punctate Palmar Plantar Keratoderma

The skin disease caused by AAGAB mutations is known as Buschke-Fischer-Brauer’s Disease or Type 1 Punctate Palmar Plantar Keratoderma (PPPK1). However, not all cases of PPPK1 are caused by AAGAB mutations.² The disease is very rare, with an estimated prevalence of 1.17 per 100,000.¹ PPPK1 is passed down from a parent to their offspring in an autosomal dominant inheritance pattern.² This means that it only takes one copy of the mutated AAGAB gene from one parent to cause PPPK1. The parent who has PPPK1 has a 50% chance of passing the mutated AAGAB gene in each pregnancy. Genetic testing is necessary to determine whether or not an individual’s symptoms of PPPK1 are caused by a mutation in the AAGAB gene.¹

Symptoms of PPPK1

Signs of PPPK1 appear in late childhood to adulthood.² Several small hyperkeratotic lesions start to appear on the palms of the hands as well as the soles of the feet. Hyperkeratotic lesions are defined papules that appear as thickening of the outer layer of skin.² The lesions typically have an irregular distribution on the palms and soles, with more lesions present on areas of the skin that are subject to higher pressure. As a person with PPPK1 grows older, they are likely to experience a greater number of lesions. This is thought to be due to mechanical or environmental stressors rather than the actual aging process.² Nail changes are rare in people who have PPPK1, although they can occur in some cases.³

IPCRR Data for AAGAB

Palmar Keratoderma	75%
Always (never goes away)	75%
Sometimes (clears up at times)	0%
Seldom (hands usually clear)	0%

Data from 2022 Sample Size N=8

References

1. Gómez-García AC, Salas-Alanís JC, Bar-Fernandez N, Mendoza-Meza R, Díaz-Montes SM, Fajardo-Ramírez OR. A novel AAGAB mutation in a Peruvian family with punctate palmoplantar keratoderma. Acta Dermatovenerol Alp Pannonica Adriat. 2021;30(1):47-48.
2. Elhaji Y, Hedlin C, Nath A, et al. AAGAB Mutations in 18 Canadian Families With Punctate Palmoplantar Keratoderma and a Possible Link to Cancer. J Cutan Med Surg. 2020;24(1):28-32. doi:10.1177/1203475419878161
3. Furniss M, Higgins CA, Martinez-Mir A, et al. Identification of distinct mutations in AAGAB in families with type 1 punctate palmoplantar keratoderma. J Invest Dermatol. 2014;134(6):1749-1752. doi:10.1038/jid.2014.

Above photos are from individuals in the IPCRR with confirmed AAGAB mutations.