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Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency
5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is a folate metabolism disorder known as a rare autosomal recessive neurodevelopmental disorder (MIM: #618367). With central nervous system involvements, it is mainly characterized by developmental delay, epilepsy, microcephaly, hypertonia,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545881/ https://www.ncbi.nlm.nih.gov/pubmed/37795244 http://dx.doi.org/10.3389/fgene.2023.1236849 |
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author | Xu, Xiaoyan Zhu, Jing Fang, Liwei Zou, Zhuo Yuan, Jingjing Peng, Min Yu, Guoliang Wu, De Liu, Yun Tang, Jiulai |
author_facet | Xu, Xiaoyan Zhu, Jing Fang, Liwei Zou, Zhuo Yuan, Jingjing Peng, Min Yu, Guoliang Wu, De Liu, Yun Tang, Jiulai |
author_sort | Xu, Xiaoyan |
collection | PubMed |
description | 5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is a folate metabolism disorder known as a rare autosomal recessive neurodevelopmental disorder (MIM: #618367). With central nervous system involvements, it is mainly characterized by developmental delay, epilepsy, microcephaly, hypertonia, and cranial nerves involvement. Here, we report three new cases with MTHFS deficiency from two non-consanguineous Chinese families. All patients showed white matter dysplasia and global developmental delay, of which only patient 1 and 2 manifested tonic-clonic seizures. Moreover, patient 2 had severe eczema and patient 3 had recurrent diarrhea. Both phenotypic features are firstly found in MTHFS deficiency. Trio whole-exome sequencing and sanger sequencing were used to identify four novel variants, p.Y169Tfs*17, p.S53F, c.117+1delG, and p.E61G in the MTHFS gene. The identification of four novel pathogenic variants and varied clinical features in three affected patients expands the genotype and phenotype spectrum of MTHFS deficiency. We also reviewed all cases of MTHFS deficiency that had previously been reported. The experience of diagnosis and treatment from these cases provides us a more comprehensive understanding of this rare disease. |
format | Online Article Text |
id | pubmed-10545881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105458812023-10-04 Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency Xu, Xiaoyan Zhu, Jing Fang, Liwei Zou, Zhuo Yuan, Jingjing Peng, Min Yu, Guoliang Wu, De Liu, Yun Tang, Jiulai Front Genet Genetics 5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is a folate metabolism disorder known as a rare autosomal recessive neurodevelopmental disorder (MIM: #618367). With central nervous system involvements, it is mainly characterized by developmental delay, epilepsy, microcephaly, hypertonia, and cranial nerves involvement. Here, we report three new cases with MTHFS deficiency from two non-consanguineous Chinese families. All patients showed white matter dysplasia and global developmental delay, of which only patient 1 and 2 manifested tonic-clonic seizures. Moreover, patient 2 had severe eczema and patient 3 had recurrent diarrhea. Both phenotypic features are firstly found in MTHFS deficiency. Trio whole-exome sequencing and sanger sequencing were used to identify four novel variants, p.Y169Tfs*17, p.S53F, c.117+1delG, and p.E61G in the MTHFS gene. The identification of four novel pathogenic variants and varied clinical features in three affected patients expands the genotype and phenotype spectrum of MTHFS deficiency. We also reviewed all cases of MTHFS deficiency that had previously been reported. The experience of diagnosis and treatment from these cases provides us a more comprehensive understanding of this rare disease. Frontiers Media S.A. 2023-09-18 /pmc/articles/PMC10545881/ /pubmed/37795244 http://dx.doi.org/10.3389/fgene.2023.1236849 Text en Copyright © 2023 Xu, Zhu, Fang, Zou, Yuan, Peng, Yu, Wu, Liu and Tang. 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 Xu, Xiaoyan Zhu, Jing Fang, Liwei Zou, Zhuo Yuan, Jingjing Peng, Min Yu, Guoliang Wu, De Liu, Yun Tang, Jiulai Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency |
title | Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency |
title_full | Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency |
title_fullStr | Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency |
title_full_unstemmed | Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency |
title_short | Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency |
title_sort | exome sequencing identified novel variants in three chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545881/ https://www.ncbi.nlm.nih.gov/pubmed/37795244 http://dx.doi.org/10.3389/fgene.2023.1236849 |
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