Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission.
Adult
Aged
Carcinoma, Adenoid Cystic
/ genetics
Deubiquitinating Enzyme CYLD
/ genetics
Diagnosis, Differential
Genetic Predisposition to Disease
Germ-Line Mutation
/ genetics
Humans
Middle Aged
Mosaicism
Neoplastic Syndromes, Hereditary
/ epidemiology
Polymerase Chain Reaction
/ methods
Prognosis
Retrospective Studies
Sampling Studies
Skin Neoplasms
/ epidemiology
Brooke-Spiegler syndrome
CYLD
CYLD cutaneous syndrome
genetic counseling
genetic testing of the skin
mosaicism
parent-to-child transmission
Journal
Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
22
02
2019
revised:
30
04
2019
accepted:
07
05
2019
pmc-release:
01
12
2019
pubmed:
16
5
2019
medline:
15
4
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
Clusters of rare cylindroma or spiradenoma tumors are a recurrent clinical presentation, yet conventional genetic testing results in individuals with these tumors are frequently normal. To determine if genetic mosaicism accounts for such cases. A study of 6 cases from a series of 55 patients who met criteria for diagnostic gene testing for pathogenic CYLD variants over a 5-year period (2012-2017) was performed. A novel genetic assay was used to study DNA from peripheral blood leukocytes and, where possible, matched skin and tumor tissue. Two patients had mosaic pathogenic CYLD variants in both the blood and skin. One of these patients transmitted a pathogenic variant to her daughter, and we report the novel phenotype of a contiguous gene deletion syndrome involving CYLD. Two patients had recurrent pathogenic variants in skin tumors from a single cluster but none detectable in the blood. The remaining 2 patients had clinical features of mosaicism, but these cases were not solved with the assays used because of a lack of access of fresh tumor tissue. Genetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients.
Sections du résumé
BACKGROUND
BACKGROUND
Clusters of rare cylindroma or spiradenoma tumors are a recurrent clinical presentation, yet conventional genetic testing results in individuals with these tumors are frequently normal.
OBJECTIVE
OBJECTIVE
To determine if genetic mosaicism accounts for such cases.
METHODS
METHODS
A study of 6 cases from a series of 55 patients who met criteria for diagnostic gene testing for pathogenic CYLD variants over a 5-year period (2012-2017) was performed. A novel genetic assay was used to study DNA from peripheral blood leukocytes and, where possible, matched skin and tumor tissue.
RESULTS
RESULTS
Two patients had mosaic pathogenic CYLD variants in both the blood and skin. One of these patients transmitted a pathogenic variant to her daughter, and we report the novel phenotype of a contiguous gene deletion syndrome involving CYLD. Two patients had recurrent pathogenic variants in skin tumors from a single cluster but none detectable in the blood.
LIMITATIONS
CONCLUSIONS
The remaining 2 patients had clinical features of mosaicism, but these cases were not solved with the assays used because of a lack of access of fresh tumor tissue.
CONCLUSION
CONCLUSIONS
Genetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients.
Identifiants
pubmed: 31085270
pii: S0190-9622(19)30784-4
doi: 10.1016/j.jaad.2019.05.021
pmc: PMC6878220
pii:
doi:
Substances chimiques
CYLD protein, human
EC 3.4.19.12
Deubiquitinating Enzyme CYLD
EC 3.4.19.12
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1300-1307Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
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