Systematic mutation screening of KRT5 supports the hypothesis that Galli-Galli disease is a variant of Dowling-Degos disease

Abstract

We found further evidence to suggest that GGD is indeed a variant of DDD and not a distinct disease entity. Two facts in particular support this conclusion: the same KRT5 mutation was found in patients with GGD and in patients with DDD, and acantholysis seems to be present in a large number of patients who had previously been assigned a diagnosis of DDD.

Mutations in POGLUT1, Encoding Protein O-Glucosyltransferase 1, Cause Autosomal-Dominant Dowling-Degos Disease

“…The clinical presentation and the genetic backgrounds of these individuals indicated that GGD is a variant of DDD and not a distinct disease entity. 6,10,11 Another locus for DDD was identified in an affected Chinese family; this locus is on chromosome 17p13.3, but the responsible mutation has not been identified to date. 12 Additionally, recent studies of two Chinese families with DDD led to the identification of mutations in POFUT1 (MIM 607491), which encodes protein O-fucosyltransferase 1 from the Notch pathway.…”

“…[5][6][7][8] In subsequent years, we screened more than 40 individuals with DDD and found KRT5 mutations in fewer than 50%, with only 16 simplex and familial cases. 9,10 Thus, the causes of a large number of unsolved cases of DDD remain to be explained. In some individuals with DDD, who had originally been diagnosed with Galli-Galli disease (GGD), the additional histopathological feature of acantholysis was observed.…”

Mutations inPOGLUT1in Galli–Galli/Dowling–Degos disease

“…In light of substantial clinical, histological and mutational overlap between GGD and DDD, they are considered to belong to the same entity 2, 3. Mutations in KRT5 (encoding keratin 5) have been associated with GGD/DDD since 2006 2, 3, 4, 5.…”

Galli-Galli disease is an acantholytic variant of Dowling-Degos disease: Additional genetic evidence in a German family

“…4 These findings indicate that GGD is not a distinct disease, but rather a variant of DDD predisposing to acantholysis. The missense mutation c.418dupA, which is the most common mutation identified for DDD/GGD, leads to a premature stop codon and consequently a truncated KRT5.…”