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Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family
Schizophrenia is a complex genetic disorder involving many common variants with modest effects and rare mutations with high penetrance. Rare mutations associated with schizophrenia are highly heterogeneous and private for affected individuals and families. Identifying such mutations can help establi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707139/ https://www.ncbi.nlm.nih.gov/pubmed/34945726 http://dx.doi.org/10.3390/jpm11121254 |
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author | Chen, Chia-Hsiang Huang, Ailing Huang, Yu-Shu Fang, Ting-Hsuan |
author_facet | Chen, Chia-Hsiang Huang, Ailing Huang, Yu-Shu Fang, Ting-Hsuan |
author_sort | Chen, Chia-Hsiang |
collection | PubMed |
description | Schizophrenia is a complex genetic disorder involving many common variants with modest effects and rare mutations with high penetrance. Rare mutations associated with schizophrenia are highly heterogeneous and private for affected individuals and families. Identifying such mutations can help establish the molecular diagnosis, elucidate the pathogenesis, and provide helpful genetic counseling for affected patients and families. We performed a whole-exome sequencing analysis to search for rare pathogenic mutations co-segregating with schizophrenia transmitted in a dominant inheritance in a two-generation multiplex family. We identified a rare missense mutation H1574R (Histidine1574Arginine, rs199796552) of KMT2C (lysine methyltransferase 2C) co-segregating with affected members in this family. The mutation is a novel deleterious mutation of KMT2C, not reported before in the literature. The KMT2C encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase and involves epigenetic regulation of brain gene expression. Mutations of KMT2C have been found in neurodevelopmental disorders, such as Kleefstra syndrome, intellectual disability, and autism spectrum disorders. Our finding suggests that schizophrenia might be one of the clinical phenotype spectra of KMT2C mutations, and KMT2C might be a novel risk gene for schizophrenia. Nevertheless, the co-segregation of this mutation with schizophrenia in this family might also be due to chance; functional assays of this mutation are needed to address this issue. |
format | Online Article Text |
id | pubmed-8707139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87071392021-12-25 Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family Chen, Chia-Hsiang Huang, Ailing Huang, Yu-Shu Fang, Ting-Hsuan J Pers Med Article Schizophrenia is a complex genetic disorder involving many common variants with modest effects and rare mutations with high penetrance. Rare mutations associated with schizophrenia are highly heterogeneous and private for affected individuals and families. Identifying such mutations can help establish the molecular diagnosis, elucidate the pathogenesis, and provide helpful genetic counseling for affected patients and families. We performed a whole-exome sequencing analysis to search for rare pathogenic mutations co-segregating with schizophrenia transmitted in a dominant inheritance in a two-generation multiplex family. We identified a rare missense mutation H1574R (Histidine1574Arginine, rs199796552) of KMT2C (lysine methyltransferase 2C) co-segregating with affected members in this family. The mutation is a novel deleterious mutation of KMT2C, not reported before in the literature. The KMT2C encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase and involves epigenetic regulation of brain gene expression. Mutations of KMT2C have been found in neurodevelopmental disorders, such as Kleefstra syndrome, intellectual disability, and autism spectrum disorders. Our finding suggests that schizophrenia might be one of the clinical phenotype spectra of KMT2C mutations, and KMT2C might be a novel risk gene for schizophrenia. Nevertheless, the co-segregation of this mutation with schizophrenia in this family might also be due to chance; functional assays of this mutation are needed to address this issue. MDPI 2021-11-25 /pmc/articles/PMC8707139/ /pubmed/34945726 http://dx.doi.org/10.3390/jpm11121254 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Chia-Hsiang Huang, Ailing Huang, Yu-Shu Fang, Ting-Hsuan Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family |
title | Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family |
title_full | Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family |
title_fullStr | Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family |
title_full_unstemmed | Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family |
title_short | Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family |
title_sort | identification of a rare novel kmt2c mutation that presents with schizophrenia in a multiplex family |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707139/ https://www.ncbi.nlm.nih.gov/pubmed/34945726 http://dx.doi.org/10.3390/jpm11121254 |
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