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Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants
BACKGROUND: Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly. RESULTS: We enrolled 24 patients with isola...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556951/ https://www.ncbi.nlm.nih.gov/pubmed/33054853 http://dx.doi.org/10.1186/s13023-020-01572-9 |
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author | Tian, Wen Huang, Yingzhao Sun, Liying Guo, Yang Zhao, Sen Lin, Mao Dong, Xiying Zhong, Wenyao Yin, Yuehan Chen, Zefu Zhang, Nan Zhang, Yuanqiang Wang, Lianlei Lin, Jiachen Yan, Zihui Yang, Xinzhuang Zhao, Junhui Qiu, Guixing Zhang, Jianguo Wu, Zhihong Wu, Nan |
author_facet | Tian, Wen Huang, Yingzhao Sun, Liying Guo, Yang Zhao, Sen Lin, Mao Dong, Xiying Zhong, Wenyao Yin, Yuehan Chen, Zefu Zhang, Nan Zhang, Yuanqiang Wang, Lianlei Lin, Jiachen Yan, Zihui Yang, Xinzhuang Zhao, Junhui Qiu, Guixing Zhang, Jianguo Wu, Zhihong Wu, Nan |
author_sort | Tian, Wen |
collection | PubMed |
description | BACKGROUND: Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly. RESULTS: We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease. Targeted next-generation sequencing was performed using patients’ blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype–phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005). CONCLUSIONS: Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly. |
format | Online Article Text |
id | pubmed-7556951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75569512020-10-15 Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants Tian, Wen Huang, Yingzhao Sun, Liying Guo, Yang Zhao, Sen Lin, Mao Dong, Xiying Zhong, Wenyao Yin, Yuehan Chen, Zefu Zhang, Nan Zhang, Yuanqiang Wang, Lianlei Lin, Jiachen Yan, Zihui Yang, Xinzhuang Zhao, Junhui Qiu, Guixing Zhang, Jianguo Wu, Zhihong Wu, Nan Orphanet J Rare Dis Research BACKGROUND: Isolated macrodactyly is a severe congenital hand anomaly with functional and physiological impact. Known causative genes include PIK3CA, AKT1 and PTEN. The aim of this study is to gain insights into the genetics basis of isolated macrodactyly. RESULTS: We enrolled 24 patients with isolated macrodactyly. Four of them were diagnosed with Proteus syndrome based on skin presentations characteristic to this disease. Targeted next-generation sequencing was performed using patients’ blood and affected tissues. Overall, 20 patients carry mosaic PIK3CA pathogenic variants, i.e. p.His1047Arg (N = 7), p.Glu542Lys (N = 6), p.Glu545Lys (N = 2), p.His1047Leu (N = 2), p.Glu453Lys (N = 1), p.Gln546Lys (N = 1) and p.His1047Tyr (N = 1). Four patients who met the diagnostic criteria of Proteus syndrome carry mosaic AKT1 p.Glu17Lys variant. Variant allele frequencies of these mosaic variants obtained through next-generation sequencing range from 10 to 33%. In genotype–phenotype correlation analysis of patients with PIK3CA variant, we found that patients with the macrodactyly of the lower limbs tend to carry PIK3CA variants located in the helical domain (P = 0.005). CONCLUSIONS: Mosaic PIK3CA and AKT1 variants can be found in all of our samples with isolated macrodactyly. Insights into phenotypic and genetic spectrum of isolated macrodactyly may be helpful in perusing a more precise and effective management of isolated macrodactyly. BioMed Central 2020-10-14 /pmc/articles/PMC7556951/ /pubmed/33054853 http://dx.doi.org/10.1186/s13023-020-01572-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Tian, Wen Huang, Yingzhao Sun, Liying Guo, Yang Zhao, Sen Lin, Mao Dong, Xiying Zhong, Wenyao Yin, Yuehan Chen, Zefu Zhang, Nan Zhang, Yuanqiang Wang, Lianlei Lin, Jiachen Yan, Zihui Yang, Xinzhuang Zhao, Junhui Qiu, Guixing Zhang, Jianguo Wu, Zhihong Wu, Nan Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants |
title | Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants |
title_full | Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants |
title_fullStr | Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants |
title_full_unstemmed | Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants |
title_short | Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants |
title_sort | phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of pik3ca and akt1 oncogenic variants |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556951/ https://www.ncbi.nlm.nih.gov/pubmed/33054853 http://dx.doi.org/10.1186/s13023-020-01572-9 |
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