Grover’s disease associated with variants in ATP2A2 gene

Key takeaways:

• 80% of Grover’s disease cases were associated with highly damaging ATP2A2 single-nucleotide variants.
• All cases were predicted to alter the encoded protein.

Grover’s disease may be associated with damaging single-nucleotide variants in the ATP2A2 gene, highlighting the role of somatic variation in acquired disorders, according to a study.

Grover’s disease, a skin condition that primarily affects the torso, bears histological similarities to Darier disease with both having focal loss of adhesion between cells and abnormal keratinization. Since Darier disease is associated with germline variants in the ATP2A2 gene, it is hypothesized that Grover’s disease is as well.

In this retrospective study compiled from a dermatopathology archive from January 2007 to December 2011, researchers determined if the damaging somatic single-nucleotide variants (SNVs) in ATP2A2 are associated with Grover’s disease.

This was done by extracting participant DNA from biopsy tissues and sequencing them with a 51-gene panel to screen for SNVs.

Results showed that of 15 cases of Grover’s disease, 12 contained SNVs in the ATP2A2 gene, all of which were C>T or G>A.

“All were predicted to alter the encoded protein and had Combined Annotation Dependent Depletion scores greater than 25, strongly supporting pathogenicity,” Devin Seli, of the department of dermatology at Yale University School of Medicine, and colleagues wrote, emphasizing the high damage in this gene.

Further results showed that of the 12 cases where SNVs were present in the tissue associated with Grover’s disease, nine cases showed ATP2A2 somatic variants that were absent from unaffected tissue DNA and three cases showed variants that were enriched fourfold to 22-fold compared with control tissue.

While the association between Grover’s disease and germline variants in the ATP2A2 gene was present, 20% of Grover’s disease cases did not show the same association. According to the authors, this may indicate that there are undetected somatic variants in this gene or other genes that may explain the lack of damaging SNVs found in Grover’s disease pathogenesis.

“The findings of this study suggest that [Grover’s disease] may be frequently associated with somatic ATP2A2-damaging SNVs and highlight the contribution of somatic variants to acquired dermatoses,” the authors concluded.