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Whole exome sequencing improves mutation detection in Hailey-Hailey disease
Zhe Wang1, Zhenzhen Wang1, Lele Sun1
1Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
The Journal of Dermatology
|April 20, 2021
Summary
Whole exome sequencing (WES) significantly improves mutation detection for Hailey-Hailey disease (HHD) patients when Sanger sequencing fails. This advanced technique identified new ATP2C1 and ATP2A2 gene mutations, increasing the overall HHD mutation detection rate.
Area of Science:
- Genetics
- Dermatology
- Molecular Biology
Background:
- Hailey-Hailey disease (HHD) is an autosomal dominant disorder linked to ATP2C1 gene defects.
- Previous Sanger sequencing methods failed to identify mutations in 12-55% of HHD patients.
- The limitations of Sanger sequencing necessitate advanced diagnostic approaches for HHD.
Purpose of the Study:
- To employ whole exome sequencing (WES) in HHD patients with previously unidentified mutations.
- To identify novel pathogenic genes responsible for HHD.
- To enhance the diagnostic yield for Hailey-Hailey disease.
Main Methods:
- Whole exome sequencing (WES) was performed on genomic DNA from 13 HHD patients.
- 364 healthy controls were included for comparison.
- Identified mutations were validated using Sanger sequencing.
Main Results:
- WES identified eight ATP2C1 gene mutations in HHD patients.
- One patient had an ATP2A2 gene mutation, associated with Darier's disease.
- The overall mutation detection rate, including prior studies, reached 90.4% (47/52 patients).
Conclusions:
- Whole exome sequencing (WES) offers superior sensitivity for detecting HHD-causing mutations compared to Sanger sequencing.
- WES facilitates the identification of mutations in genes beyond ATP2C1, broadening diagnostic capabilities.
- This study significantly increases the known mutation detection rate for Hailey-Hailey disease.
