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Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria
BACKGROUND: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hy...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137868/ https://www.ncbi.nlm.nih.gov/pubmed/30217188 http://dx.doi.org/10.1186/s12881-018-0675-9 |
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author | Peng, Wei Ma, Xiu-Wei Yang, Xiao Zhang, Wan-Qiao Yan, Lei Wang, Yong-Xia Liu, Xin Wang, Yan Feng, Zhi-Chun |
author_facet | Peng, Wei Ma, Xiu-Wei Yang, Xiao Zhang, Wan-Qiao Yan, Lei Wang, Yong-Xia Liu, Xin Wang, Yan Feng, Zhi-Chun |
author_sort | Peng, Wei |
collection | PubMed |
description | BACKGROUND: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons. CASE PRESENTATION: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic. CONCLUSION: We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations. |
format | Online Article Text |
id | pubmed-6137868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61378682018-09-15 Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria Peng, Wei Ma, Xiu-Wei Yang, Xiao Zhang, Wan-Qiao Yan, Lei Wang, Yong-Xia Liu, Xin Wang, Yan Feng, Zhi-Chun BMC Med Genet Case Report BACKGROUND: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons. CASE PRESENTATION: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic. CONCLUSION: We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations. BioMed Central 2018-09-14 /pmc/articles/PMC6137868/ /pubmed/30217188 http://dx.doi.org/10.1186/s12881-018-0675-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Case Report Peng, Wei Ma, Xiu-Wei Yang, Xiao Zhang, Wan-Qiao Yan, Lei Wang, Yong-Xia Liu, Xin Wang, Yan Feng, Zhi-Chun Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria |
title | Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria |
title_full | Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria |
title_fullStr | Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria |
title_full_unstemmed | Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria |
title_short | Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria |
title_sort | two novel l2hgdh mutations identified in a rare chinese family with l-2-hydroxyglutaric aciduria |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137868/ https://www.ncbi.nlm.nih.gov/pubmed/30217188 http://dx.doi.org/10.1186/s12881-018-0675-9 |
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