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Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism
Malan syndrome is an autosomal dominant disorder caused by pathogenic variants in NFIX with less than 100 cases reported thus far. NFIX is important for stem cell proliferation, quiescence, and differentiation during development and its protein plays a role in replication, signal transduction, and t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682143/ https://www.ncbi.nlm.nih.gov/pubmed/36437934 http://dx.doi.org/10.3389/fgene.2022.1044660 |
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author | Langley, Elizabeth Farach, Laura S. Mowrey, Kate |
author_facet | Langley, Elizabeth Farach, Laura S. Mowrey, Kate |
author_sort | Langley, Elizabeth |
collection | PubMed |
description | Malan syndrome is an autosomal dominant disorder caused by pathogenic variants in NFIX with less than 100 cases reported thus far. NFIX is important for stem cell proliferation, quiescence, and differentiation during development and its protein plays a role in replication, signal transduction, and transcription. As a result of pathogenic variants, symptoms of Malan syndrome include overgrowth, intellectual disability, speech delay, and dysmorphic features. Currently, the recurrence risk for this disorder is indicated at less than 1%, standard for de novo autosomal dominant disorders. Herein, we report an additional set of sisters with the same novel pathogenic variant in NFIX and clinical features consistent with Malan syndrome providing evidence of germline mosaicism. Considering the rarity of this condition in conjunction with three previous reports of germline mosaicism, it is worthwhile to investigate and re-evaluate the proper recurrence risk for this condition. This discovery would be paramount for family planning and genetic counseling practices in families with affected individuals. |
format | Online Article Text |
id | pubmed-9682143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96821432022-11-24 Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism Langley, Elizabeth Farach, Laura S. Mowrey, Kate Front Genet Genetics Malan syndrome is an autosomal dominant disorder caused by pathogenic variants in NFIX with less than 100 cases reported thus far. NFIX is important for stem cell proliferation, quiescence, and differentiation during development and its protein plays a role in replication, signal transduction, and transcription. As a result of pathogenic variants, symptoms of Malan syndrome include overgrowth, intellectual disability, speech delay, and dysmorphic features. Currently, the recurrence risk for this disorder is indicated at less than 1%, standard for de novo autosomal dominant disorders. Herein, we report an additional set of sisters with the same novel pathogenic variant in NFIX and clinical features consistent with Malan syndrome providing evidence of germline mosaicism. Considering the rarity of this condition in conjunction with three previous reports of germline mosaicism, it is worthwhile to investigate and re-evaluate the proper recurrence risk for this condition. This discovery would be paramount for family planning and genetic counseling practices in families with affected individuals. Frontiers Media S.A. 2022-11-09 /pmc/articles/PMC9682143/ /pubmed/36437934 http://dx.doi.org/10.3389/fgene.2022.1044660 Text en Copyright © 2022 Langley, Farach and Mowrey. https://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 Langley, Elizabeth Farach, Laura S. Mowrey, Kate Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism |
title | Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism |
title_full | Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism |
title_fullStr | Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism |
title_full_unstemmed | Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism |
title_short | Case Report: Novel pathogenic variant in NFIX in two sisters with Malan syndrome due to germline mosaicism |
title_sort | case report: novel pathogenic variant in nfix in two sisters with malan syndrome due to germline mosaicism |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682143/ https://www.ncbi.nlm.nih.gov/pubmed/36437934 http://dx.doi.org/10.3389/fgene.2022.1044660 |
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