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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...

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Autores principales: Langley, Elizabeth, Farach, Laura S., Mowrey, Kate
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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