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Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report

BACKGROUND: The proto-oncogene KRAS performs an essential function in normal tissue signaling, and the mutation of KRAS gene is a key step in the development of many cancers. Somatic KRAS mutations are often detected in patients with solid and non-solid tumors, whereas germline KRAS mutations are im...

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Autores principales: Yao, Ruen, Yu, Tingting, Xu, Yufei, Li, Guoqiang, Yin, Lei, Zhou, Yunfang, Wang, Jian, Yan, Zhilong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048798/
https://www.ncbi.nlm.nih.gov/pubmed/30012129
http://dx.doi.org/10.1186/s12920-018-0377-3
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author Yao, Ruen
Yu, Tingting
Xu, Yufei
Li, Guoqiang
Yin, Lei
Zhou, Yunfang
Wang, Jian
Yan, Zhilong
author_facet Yao, Ruen
Yu, Tingting
Xu, Yufei
Li, Guoqiang
Yin, Lei
Zhou, Yunfang
Wang, Jian
Yan, Zhilong
author_sort Yao, Ruen
collection PubMed
description BACKGROUND: The proto-oncogene KRAS performs an essential function in normal tissue signaling, and the mutation of KRAS gene is a key step in the development of many cancers. Somatic KRAS mutations are often detected in patients with solid and non-solid tumors, whereas germline KRAS mutations are implicated in patients with the Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome and Costello syndrome. The deletion of chromosome 10q22.3-q23.2 is a rare cytogenetic abnormality, which often leads to distinct facial appearance and delays in speech and global development. CASE PRESENTATION: Herein, we report the case of a 4-year-old boy diagnosed with juvenile myelomonocytic leukemia. The boy also had syndromic features, such as speech and motor developmental delay, multiple congenital malformations, including distinct facial features, club feet, and cryptorchidism. Using whole-exome sequencing, we identified a pathogenic mutation in KRAS [c.34G > A, p.Gly12Ser] isolated from peripheral blood DNA. Sanger sequencing confirmed the wild-type sequence in the parents and patient’s salivary cell DNA indicating its somatic state. A 7311-kb deletion in 10q22.3-q23.2 was also revealed by chromosomal microarray analysis, which was later proved as a germline de novo variant. CONCLUSION: Juvenile myelomonocytic leukemia in the patient was attributed to a somatic KRAS mutation, whereas the syndromic features of the patient were considered a consequence of germline chromosome 10q22.3-q23.2 deletion. Genetic testing for patients with complicated phenotypes can be valuable in detecting multiple pathogenic variants.
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spelling pubmed-60487982018-07-19 Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report Yao, Ruen Yu, Tingting Xu, Yufei Li, Guoqiang Yin, Lei Zhou, Yunfang Wang, Jian Yan, Zhilong BMC Med Genomics Case Report BACKGROUND: The proto-oncogene KRAS performs an essential function in normal tissue signaling, and the mutation of KRAS gene is a key step in the development of many cancers. Somatic KRAS mutations are often detected in patients with solid and non-solid tumors, whereas germline KRAS mutations are implicated in patients with the Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome and Costello syndrome. The deletion of chromosome 10q22.3-q23.2 is a rare cytogenetic abnormality, which often leads to distinct facial appearance and delays in speech and global development. CASE PRESENTATION: Herein, we report the case of a 4-year-old boy diagnosed with juvenile myelomonocytic leukemia. The boy also had syndromic features, such as speech and motor developmental delay, multiple congenital malformations, including distinct facial features, club feet, and cryptorchidism. Using whole-exome sequencing, we identified a pathogenic mutation in KRAS [c.34G > A, p.Gly12Ser] isolated from peripheral blood DNA. Sanger sequencing confirmed the wild-type sequence in the parents and patient’s salivary cell DNA indicating its somatic state. A 7311-kb deletion in 10q22.3-q23.2 was also revealed by chromosomal microarray analysis, which was later proved as a germline de novo variant. CONCLUSION: Juvenile myelomonocytic leukemia in the patient was attributed to a somatic KRAS mutation, whereas the syndromic features of the patient were considered a consequence of germline chromosome 10q22.3-q23.2 deletion. Genetic testing for patients with complicated phenotypes can be valuable in detecting multiple pathogenic variants. BioMed Central 2018-07-16 /pmc/articles/PMC6048798/ /pubmed/30012129 http://dx.doi.org/10.1186/s12920-018-0377-3 Text en © The Author(s). 2018 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 Case Report
Yao, Ruen
Yu, Tingting
Xu, Yufei
Li, Guoqiang
Yin, Lei
Zhou, Yunfang
Wang, Jian
Yan, Zhilong
Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report
title Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report
title_full Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report
title_fullStr Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report
title_full_unstemmed Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report
title_short Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report
title_sort concurrent somatic kras mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048798/
https://www.ncbi.nlm.nih.gov/pubmed/30012129
http://dx.doi.org/10.1186/s12920-018-0377-3
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