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Phenotypic distinctions between mosaic forms of tuberous sclerosis complex
- Source :
- Genetics in medicine : official journal of the American College of Medical Genetics
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Purpose: To determine if mosaic tuberous sclerosis complex (TSC) can be stratified into subtypes that correspond with prognosis and extent of disease. Methods: Next-generation sequencing of skin tumor and other samples was used to identify patients with mosaic pathogenic variants in TSC1 or TSC2. Extent of disease, onset age, and family history of TSC were determined through retrospective analysis of patient records. Results: The median number of disease findings and age at penetrance differed between mosaic patients with asymmetrically distributed facial angiofibromas (4 findings, 24y, n=7), mosaic patients with bilaterally symmetric facial angiofibromas (8 findings, 10y, n=12), and germline TSC patients (10 findings, 4y, n=29). Cutaneous and internal organ involvement positively correlated in mosaic (R=0.62, p=0.005), but not germline (R=−0.24, p=0.24) TSC. Variant allele fraction (VAF) in the blood (range: 0-19%) positively correlated with the number of major features (R=0.55, p=0.028). Five had a TSC2 variant identified in the skin that was below detection in the blood. One of 12 children from a mosaic parent had TSC. Conclusion: The phenotype of mosaic TSC ranged from mild to indistinguishable from germline disease. Patients with mosaicism and asymmetric facial angiofibromas exhibited fewer findings, later onset, and lower VAF in the blood.
- Subjects :
- Adult
Male
congenital, hereditary, and neonatal diseases and abnormalities
Pathology
medicine.medical_specialty
Skin Neoplasms
Segmental
Angiofibroma
Article
Tuberous Sclerosis Complex 1 Protein
Germline
Tuberous sclerosis
Tuberous Sclerosis
Tuberous Sclerosis Complex 2 Protein
medicine
Humans
Genodermatosis
Family history
Genetics (clinical)
Retrospective Studies
Mosaicism
business.industry
Tumor Suppressor Proteins
High-Throughput Nucleotide Sequencing
Middle Aged
medicine.disease
Penetrance
Phenotype
medicine.anatomical_structure
Tuberous sclerosis complex
Mutation
Female
TSC1
TSC2
business
Mosaic
Subjects
Details
- ISSN :
- 10983600
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Genetics in Medicine
- Accession number :
- edsair.doi.dedup.....b5d9d906a92881f61381e2fe93664463