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Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission

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: To determine if genetic mosaicism accounts for such cases. METHODS: A study of 6 cases from...

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Autores principales: Arefi, Majid, Wilson, Valerie, Muthiah, Siobhan, Zwolinski, Simon, Bajwa, Dalvir, Brennan, Paul, Blasdale, Katie, Bourn, David, Burn, John, Santibanez-Koref, Mauro, Rajan, Neil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mosby 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878220/
https://www.ncbi.nlm.nih.gov/pubmed/31085270
http://dx.doi.org/10.1016/j.jaad.2019.05.021
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author Arefi, Majid
Wilson, Valerie
Muthiah, Siobhan
Zwolinski, Simon
Bajwa, Dalvir
Brennan, Paul
Blasdale, Katie
Bourn, David
Burn, John
Santibanez-Koref, Mauro
Rajan, Neil
author_facet Arefi, Majid
Wilson, Valerie
Muthiah, Siobhan
Zwolinski, Simon
Bajwa, Dalvir
Brennan, Paul
Blasdale, Katie
Bourn, David
Burn, John
Santibanez-Koref, Mauro
Rajan, Neil
author_sort Arefi, Majid
collection PubMed
description 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: To determine if genetic mosaicism accounts for such cases. 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: 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: 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: Genetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients.
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spelling pubmed-68782202019-12-01 Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission Arefi, Majid Wilson, Valerie Muthiah, Siobhan Zwolinski, Simon Bajwa, Dalvir Brennan, Paul Blasdale, Katie Bourn, David Burn, John Santibanez-Koref, Mauro Rajan, Neil J Am Acad Dermatol Article 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: To determine if genetic mosaicism accounts for such cases. 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: 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: 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: Genetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients. Mosby 2019-12 /pmc/articles/PMC6878220/ /pubmed/31085270 http://dx.doi.org/10.1016/j.jaad.2019.05.021 Text en © 2019 by the American Academy of Dermatology, Inc. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arefi, Majid
Wilson, Valerie
Muthiah, Siobhan
Zwolinski, Simon
Bajwa, Dalvir
Brennan, Paul
Blasdale, Katie
Bourn, David
Burn, John
Santibanez-Koref, Mauro
Rajan, Neil
Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission
title Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission
title_full Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission
title_fullStr Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission
title_full_unstemmed Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission
title_short Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission
title_sort diverse presentations of cutaneous mosaicism occur in cyld cutaneous syndrome and may result in parent-to-child transmission
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878220/
https://www.ncbi.nlm.nih.gov/pubmed/31085270
http://dx.doi.org/10.1016/j.jaad.2019.05.021
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