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Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping

Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility in identification of clinical likely pathogenic variants needs to be further demonstrated and proved. In a family with two consecutive pregnancies affected wi...

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Autores principales: Chen, Min, Zhang, Min, Qian, Yeqing, Yang, Yanmei, Sun, Yixi, Liu, Bei, Wang, Liya, Dong, Minyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538933/
https://www.ncbi.nlm.nih.gov/pubmed/33083009
http://dx.doi.org/10.1038/s41525-020-0138-z
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author Chen, Min
Zhang, Min
Qian, Yeqing
Yang, Yanmei
Sun, Yixi
Liu, Bei
Wang, Liya
Dong, Minyue
author_facet Chen, Min
Zhang, Min
Qian, Yeqing
Yang, Yanmei
Sun, Yixi
Liu, Bei
Wang, Liya
Dong, Minyue
author_sort Chen, Min
collection PubMed
description Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility in identification of clinical likely pathogenic variants needs to be further demonstrated and proved. In a family with two consecutive pregnancies affected with ventriculomegaly, a splicing likely pathogenic variant at the LAMA1 locus (NM_005559: c. 4663 + 1 G > C) inherited from the father was identified in the proband by whole-exome sequencing, and no other pathogenic variant associated with the clinical phenotypes was detected. SV analysis by BOM revealed an ~48 kb duplication at the LAMA1 locus in the maternal sample. Real-time quantitative PCR and Sanger sequencing further confirmed the duplication as c.859-153_4806 + 910dup. Based on these variants, we hypothesize that the fetuses have Poretti-Boltshauser syndrome (PBS) presenting with ventriculomegaly. With the ability to determine single nucleotide variants and SVs, the strategy adopted here might be useful to detect cases missed by current routine screening methods. In addition, our study may broaden the phenotypic spectrum of fetuses with PBS.
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spelling pubmed-75389332020-10-19 Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping Chen, Min Zhang, Min Qian, Yeqing Yang, Yanmei Sun, Yixi Liu, Bei Wang, Liya Dong, Minyue NPJ Genom Med Case Report Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility in identification of clinical likely pathogenic variants needs to be further demonstrated and proved. In a family with two consecutive pregnancies affected with ventriculomegaly, a splicing likely pathogenic variant at the LAMA1 locus (NM_005559: c. 4663 + 1 G > C) inherited from the father was identified in the proband by whole-exome sequencing, and no other pathogenic variant associated with the clinical phenotypes was detected. SV analysis by BOM revealed an ~48 kb duplication at the LAMA1 locus in the maternal sample. Real-time quantitative PCR and Sanger sequencing further confirmed the duplication as c.859-153_4806 + 910dup. Based on these variants, we hypothesize that the fetuses have Poretti-Boltshauser syndrome (PBS) presenting with ventriculomegaly. With the ability to determine single nucleotide variants and SVs, the strategy adopted here might be useful to detect cases missed by current routine screening methods. In addition, our study may broaden the phenotypic spectrum of fetuses with PBS. Nature Publishing Group UK 2020-08-12 /pmc/articles/PMC7538933/ /pubmed/33083009 http://dx.doi.org/10.1038/s41525-020-0138-z Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Case Report
Chen, Min
Zhang, Min
Qian, Yeqing
Yang, Yanmei
Sun, Yixi
Liu, Bei
Wang, Liya
Dong, Minyue
Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping
title Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping
title_full Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping
title_fullStr Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping
title_full_unstemmed Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping
title_short Identification of a likely pathogenic structural variation in the LAMA1 gene by Bionano optical mapping
title_sort identification of a likely pathogenic structural variation in the lama1 gene by bionano optical mapping
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538933/
https://www.ncbi.nlm.nih.gov/pubmed/33083009
http://dx.doi.org/10.1038/s41525-020-0138-z
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