USA: Genetic analysis of a cohort of patients with the disease suggests that somatic single-nucleotide variants (SNVs) in ATP2A2 are often linked with Grover disease (GD). The findings were published online in JAMA Dermatology on May 17, 2023.
The discovery highlights the role of somatic variation in acquired disorders. The retrospective case series employing archival tissue from 15 patients with Grover disease revealed that 80% were associated with damaging SNVs in ATP2A2. All variants were G>A or C>T substitutions, indicating that UV light-induced mutagenesis may contribute to lesion development.

Transient acantholytic dermatosis, commonly called Grover disease, manifests as papulovesicles, papules, and small nodules that appear on the torso more often than the limbs of affected patients, typically occurring in older individuals. Irradiation, sweating, medications, cancers, organ transplantation, and kidney failure exacerbate it. The pathobiology of Grover's disease remains unknown.
Devin Seli, Yale University School of Medicine, New Haven, Connecticut, and colleagues aimed to determine if damaging somatic single-nucleotide variants are associated with Grover disease.
The researchers identified consecutive patients from a dermatopathology archive for four years who had one biopsy with a clinical diagnosis of Grover disease confirmed via histopathologic findings and another non-GD biopsy. DNA from the participants were extracted from both biopsy tissues and sequenced to high depth with a 51-gene panel for SNVs screening in genes previously linked with acantholysis and Mendelian cornification disorders.
They employed comparative analysis of sequencing data from paired GD and control tissue to identify SNVs predicted to impact gene function, which was highly enriched, or exclusive in, GD tissue.
The authors reported the following findings:
12 of 15 cases of GD (12 men and three women; mean age, 68.3 years) were associated with C>T or G>A ATP2A2 SNVs in GD tissue; all were predicted to be highly damaging via combined annotation-dependent depletion (CADD) scores, and four were previously associated with Darier disease.
In 75% of the cases, the GD-associated ATP2A2 SNV was absent from control tissue DNA, and in 25% of cases, ATP2A2 SNVs were enriched 4- to 22-fold in GD vs control tissue.
"The finding that 20% of GD cases did not have associated ATP2A2 damaging SNVs indicates that there may be undetected somatic variants in ATP2A2 or other genes and explains the ATP2A2-damaging SNVs absence found in prior genetic studies of GD pathogenesis," the researchers wrote. They added that future GD studies might reveal additional somatic damaging SNVs in other genes linked with acantholysis.
"The study's findings suggest that GD may be frequently associated with somatic ATP2A2-damaging SNVs and underscore the contribution of somatic variants to acquired dermatoses," they concluded.
Reference:
Seli D, Ellis KT, Goldust M, et al. Association of Somatic ATP2A2 Damaging Variants With Grover Disease. JAMA Dermatol. Published online May 17, 2023. doi:10.1001/jamadermatol.2023.1139