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Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders

BACKGROUND: Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagn...

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Autores principales: Xu, Shanshan, Fan, Yanjie, Sun, Yu, Wang, Lili, Gu, Xuefan, Yu, Yongguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663114/
https://www.ncbi.nlm.nih.gov/pubmed/29084544
http://dx.doi.org/10.1186/s12920-017-0298-6
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author Xu, Shanshan
Fan, Yanjie
Sun, Yu
Wang, Lili
Gu, Xuefan
Yu, Yongguo
author_facet Xu, Shanshan
Fan, Yanjie
Sun, Yu
Wang, Lili
Gu, Xuefan
Yu, Yongguo
author_sort Xu, Shanshan
collection PubMed
description BACKGROUND: Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES). METHODS: TS/WES was performed to identify mutations in ten Chinese patients who exhibited the following manifestations: potential facial dysmorphisms, short stature, congenital heart defects, and developmental delay. Sanger sequencing was used to confirm the suspected pathological variants in the patients and their family members. RESULTS: TS/WES revealed three mutations in the PTPN11 gene, three mutations in RAF1 gene, and four mutations in BRAF gene in the NS and NSML patients who were previously diagnosed based on the abovementioned clinical features. All the identified mutations were determined to be de novo mutations. However, two patients who carried the same mutation in the RAF1 gene presented different clinical features. One patient with multiple lentigines was diagnosed with NSML, while the other patient without lentigines was diagnosed with NS. In addition, a patient who carried a hotspot mutation in the BRAF gene was diagnosed with NS instead of cardiofaciocutaneous syndrome (CFCS). CONCLUSIONS: TS/WES has emerged as a useful tool for definitive diagnosis and accurate genetic counseling of atypical cases. In this study, we analyzed ten Chinese patients diagnosed with NS and related disorders and identified their correspondingPTPN11, RAF1, and BRAF mutations. Among the target genes, BRAF showed the same degree of correlation with NS incidence as that of PTPN11 or RAF1.
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spelling pubmed-56631142017-11-01 Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders Xu, Shanshan Fan, Yanjie Sun, Yu Wang, Lili Gu, Xuefan Yu, Yongguo BMC Med Genomics Research Article BACKGROUND: Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES). METHODS: TS/WES was performed to identify mutations in ten Chinese patients who exhibited the following manifestations: potential facial dysmorphisms, short stature, congenital heart defects, and developmental delay. Sanger sequencing was used to confirm the suspected pathological variants in the patients and their family members. RESULTS: TS/WES revealed three mutations in the PTPN11 gene, three mutations in RAF1 gene, and four mutations in BRAF gene in the NS and NSML patients who were previously diagnosed based on the abovementioned clinical features. All the identified mutations were determined to be de novo mutations. However, two patients who carried the same mutation in the RAF1 gene presented different clinical features. One patient with multiple lentigines was diagnosed with NSML, while the other patient without lentigines was diagnosed with NS. In addition, a patient who carried a hotspot mutation in the BRAF gene was diagnosed with NS instead of cardiofaciocutaneous syndrome (CFCS). CONCLUSIONS: TS/WES has emerged as a useful tool for definitive diagnosis and accurate genetic counseling of atypical cases. In this study, we analyzed ten Chinese patients diagnosed with NS and related disorders and identified their correspondingPTPN11, RAF1, and BRAF mutations. Among the target genes, BRAF showed the same degree of correlation with NS incidence as that of PTPN11 or RAF1. BioMed Central 2017-10-30 /pmc/articles/PMC5663114/ /pubmed/29084544 http://dx.doi.org/10.1186/s12920-017-0298-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
spellingShingle Research Article
Xu, Shanshan
Fan, Yanjie
Sun, Yu
Wang, Lili
Gu, Xuefan
Yu, Yongguo
Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders
title Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders
title_full Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders
title_fullStr Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders
title_full_unstemmed Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders
title_short Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders
title_sort targeted/exome sequencing identified mutations in ten chinese patients diagnosed with noonan syndrome and related disorders
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663114/
https://www.ncbi.nlm.nih.gov/pubmed/29084544
http://dx.doi.org/10.1186/s12920-017-0298-6
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