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Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing

Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testi...

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Autores principales: Zhang, Zeng-Yun-Ou, Wu, Yuan-Yuan, Cai, Xin-ying, Fang, Wen-Liang, Xiao, Feng-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985060/
https://www.ncbi.nlm.nih.gov/pubmed/33767727
http://dx.doi.org/10.3389/fgene.2021.603195
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author Zhang, Zeng-Yun-Ou
Wu, Yuan-Yuan
Cai, Xin-ying
Fang, Wen-Liang
Xiao, Feng-Li
author_facet Zhang, Zeng-Yun-Ou
Wu, Yuan-Yuan
Cai, Xin-ying
Fang, Wen-Liang
Xiao, Feng-Li
author_sort Zhang, Zeng-Yun-Ou
collection PubMed
description Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the NF1 gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3′-end of exon 30. One NF1 gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the NF2 gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis.
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spelling pubmed-79850602021-03-24 Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing Zhang, Zeng-Yun-Ou Wu, Yuan-Yuan Cai, Xin-ying Fang, Wen-Liang Xiao, Feng-Li Front Genet Genetics Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the NF1 gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3′-end of exon 30. One NF1 gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the NF2 gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis. Frontiers Media S.A. 2021-03-09 /pmc/articles/PMC7985060/ /pubmed/33767727 http://dx.doi.org/10.3389/fgene.2021.603195 Text en Copyright © 2021 Zhang, Wu, Cai, Fang and Xiao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Zhang, Zeng-Yun-Ou
Wu, Yuan-Yuan
Cai, Xin-ying
Fang, Wen-Liang
Xiao, Feng-Li
Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing
title Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing
title_full Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing
title_fullStr Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing
title_full_unstemmed Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing
title_short Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing
title_sort molecular diagnosis of neurofibromatosis by multigene panel testing
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985060/
https://www.ncbi.nlm.nih.gov/pubmed/33767727
http://dx.doi.org/10.3389/fgene.2021.603195
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