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Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family
Familial Rubinstein-Taybi syndrome (RSTS) with recurrent RSTS siblings and apparently unaffected parents is rare; such cases might result from parental somatic and/or germline mosaicism. Parental low-level (<10%) germline mosaicism in the CREBBP-associated RSTS family has not been reported. Here,...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970026/ https://www.ncbi.nlm.nih.gov/pubmed/33747050 http://dx.doi.org/10.3389/fgene.2021.640992 |
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author | Lin, Shaobin He, Zhiming Huang, Linhuan Liu, Jialiu Lei, Ting Wu, Jianzhu Huang, Peizhi Zhou, Yi Luo, Yanmin |
author_facet | Lin, Shaobin He, Zhiming Huang, Linhuan Liu, Jialiu Lei, Ting Wu, Jianzhu Huang, Peizhi Zhou, Yi Luo, Yanmin |
author_sort | Lin, Shaobin |
collection | PubMed |
description | Familial Rubinstein-Taybi syndrome (RSTS) with recurrent RSTS siblings and apparently unaffected parents is rare; such cases might result from parental somatic and/or germline mosaicism. Parental low-level (<10%) germline mosaicism in the CREBBP-associated RSTS family has not been reported. Here, we present our studies of a Chinese family with two RSTS siblings and apparently unaffected parents. We detected the apparent de novo variant (DNV) c.3235C>T (p.Gln1079(*)) in CREBBP in the siblings via trio whole-exome sequencing. High-depth next-generation sequencing (NGS) for the parents revealed a low-level (<10%) mosaic variant in both the peripheral blood (3.64%) and buccal mucosa (1.94%) of the unaffected mother, indicating maternal somatic and germline mosaicism. Peripheral blood RNA-sequencing analysis for the patients and normal individuals indicated that the c.3235C>T (p.Gln1079(*)) non-sense variant did not trigger nonsense-mediated mRNA decay to reduce CREBBP mRNA levels. Transcriptome analysis revealed 151 downregulated mRNAs and 132 upregulated mRNAs between the patients and normal individuals. This study emphasizes that high-depth NGS using multiple specimens might be applied for a family with an affected sibling caused by an apparent CREBBP DNV to identify potential low-level parental mosaicism and provide an assessment of recurrence risk. |
format | Online Article Text |
id | pubmed-7970026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79700262021-03-19 Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family Lin, Shaobin He, Zhiming Huang, Linhuan Liu, Jialiu Lei, Ting Wu, Jianzhu Huang, Peizhi Zhou, Yi Luo, Yanmin Front Genet Genetics Familial Rubinstein-Taybi syndrome (RSTS) with recurrent RSTS siblings and apparently unaffected parents is rare; such cases might result from parental somatic and/or germline mosaicism. Parental low-level (<10%) germline mosaicism in the CREBBP-associated RSTS family has not been reported. Here, we present our studies of a Chinese family with two RSTS siblings and apparently unaffected parents. We detected the apparent de novo variant (DNV) c.3235C>T (p.Gln1079(*)) in CREBBP in the siblings via trio whole-exome sequencing. High-depth next-generation sequencing (NGS) for the parents revealed a low-level (<10%) mosaic variant in both the peripheral blood (3.64%) and buccal mucosa (1.94%) of the unaffected mother, indicating maternal somatic and germline mosaicism. Peripheral blood RNA-sequencing analysis for the patients and normal individuals indicated that the c.3235C>T (p.Gln1079(*)) non-sense variant did not trigger nonsense-mediated mRNA decay to reduce CREBBP mRNA levels. Transcriptome analysis revealed 151 downregulated mRNAs and 132 upregulated mRNAs between the patients and normal individuals. This study emphasizes that high-depth NGS using multiple specimens might be applied for a family with an affected sibling caused by an apparent CREBBP DNV to identify potential low-level parental mosaicism and provide an assessment of recurrence risk. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7970026/ /pubmed/33747050 http://dx.doi.org/10.3389/fgene.2021.640992 Text en Copyright © 2021 Lin, He, Huang, Liu, Lei, Wu, Huang, Zhou and Luo. 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 Lin, Shaobin He, Zhiming Huang, Linhuan Liu, Jialiu Lei, Ting Wu, Jianzhu Huang, Peizhi Zhou, Yi Luo, Yanmin Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family |
title | Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family |
title_full | Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family |
title_fullStr | Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family |
title_full_unstemmed | Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family |
title_short | Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family |
title_sort | case report: low-level maternal mosaicism of a novel crebbp variant causes recurrent rubinstein-taybi syndrome in two siblings of a chinese family |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970026/ https://www.ncbi.nlm.nih.gov/pubmed/33747050 http://dx.doi.org/10.3389/fgene.2021.640992 |
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