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Mosaicism for ATP2A2 mutations causes segmental Darier's disease
A Sakuntabhai1, J Dhitavat, S Burge
1The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
The Journal of Investigative Dermatology
|December 20, 2000
Summary
Acantholytic dyskeratotic naevi, a skin condition following Blaschko's lines, may be caused by somatic mutations in the ATP2A2 gene. These findings suggest a link to segmental Darier's disease due to genetic mosaicism.
Area of Science:
- Dermatology
- Genetics
- Molecular Biology
Background:
- Epidermal naevi are epidermal malformations following Blaschko's lines, with genetic mosaicism proposed as a cause.
- Acantholytic epidermal naevi histologically resemble Darier's disease, a genetic skin disorder.
- The gene ATP2A2, encoding Ca(2+) ATPase, was recently identified as defective in Darier's disease.
Observation:
- This study investigated ATP2A2 gene involvement in two patients with acantholytic dyskeratotic naevi.
- Specific mutations (Y894X and G769R) in ATP2A2 were identified in the affected skin of both patients.
- These mutations were absent in unaffected skin and leukocytes, indicating somatic mutations.
Findings:
- Acantholytic dyskeratotic naevi can result from somatic mutations in the ATP2A2 gene.
- Patients with these naevi are mosaics for the identified ATP2A2 mutations.
- Blaschko's lines correlate with genetic mosaicism.
Implications:
- The findings support the concept of segmental Darier's disease caused by postzygotic mosaicism.
- The term 'acantholytic dyskeratotic naevus' may be superseded by 'segmental Darier's disease'.
- Risk of transmitting generalized Darier's disease depends on germline involvement.