Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonus
Background: Heterozygous mutations in the dehydrodolichol diphosphate synthase (DHDDS) gene are one of the causes generating developmental and epileptic encephalopathies. So far, only eleven mutations in the DHDDS gene have been identified. The mutation spectrum of the DHDDS gene in the Chinese popu...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1208540/full |
| _version_ | 1797662965362589696 |
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| author | Yi Dong Yi Zhang Yue Sheng Fang Wang Lv Liu Liang-Liang Fan |
| author_facet | Yi Dong Yi Zhang Yue Sheng Fang Wang Lv Liu Liang-Liang Fan |
| author_sort | Yi Dong |
| collection | DOAJ |
| description | Background: Heterozygous mutations in the dehydrodolichol diphosphate synthase (DHDDS) gene are one of the causes generating developmental and epileptic encephalopathies. So far, only eleven mutations in the DHDDS gene have been identified. The mutation spectrum of the DHDDS gene in the Chinese population remains unclear.Methods: In this study, we enrolled a Chinese family with myoclonus and/or epilepsy and intellectual disability. The epilepsy and myoclonic tremor were improved after deep brain stimulation (DBS) of the subthalamic nucleus (STN) treatment. Whole exome sequencing and Sanger sequencing were employed to explore the genetic variations of the family.Results: Subsequent to data filtering, we identified a recurrent pathogenic mutation (NM_001243564.1, c.113G>A/p.R38H) in the DHDDS gene in the proband. Sanger sequencing further validated that the presence of the mutation in his affected mother but absent in the health family members. Further bioinformatics analysis revealed that this mutation (p.R38H), located in an evolutionarily conserved region of DHDDS, was predicted to be deleterious.Discussion: In this report, we present the first case of intractable epilepsy and/or myoclonus caused by p.R38H mutation of the DHDDS gene in the Chinese population. Furthermore, this study represents the third report of autosomal dominant familial inheritance of DHDDS mutation worldwide. |
| first_indexed | 2024-03-11T19:07:45Z |
| format | Article |
| id | doaj.art-eb91288c84b6487ab96717e43fdeb2e8 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-11T19:07:45Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-eb91288c84b6487ab96717e43fdeb2e82023-10-10T06:26:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-10-011410.3389/fgene.2023.12085401208540Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonusYi Dong0Yi Zhang1Yue Sheng2Fang Wang3Lv Liu4Liang-Liang Fan5Department of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaMedical Psychological Center, Medical Psychological Institute of Central South University, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaDepartment of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Respiratory Medicine, Clinical Center for Gene Diagnosis and Therapy, Diagnosis and Treatment Center of Respiratory Disease, Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaBackground: Heterozygous mutations in the dehydrodolichol diphosphate synthase (DHDDS) gene are one of the causes generating developmental and epileptic encephalopathies. So far, only eleven mutations in the DHDDS gene have been identified. The mutation spectrum of the DHDDS gene in the Chinese population remains unclear.Methods: In this study, we enrolled a Chinese family with myoclonus and/or epilepsy and intellectual disability. The epilepsy and myoclonic tremor were improved after deep brain stimulation (DBS) of the subthalamic nucleus (STN) treatment. Whole exome sequencing and Sanger sequencing were employed to explore the genetic variations of the family.Results: Subsequent to data filtering, we identified a recurrent pathogenic mutation (NM_001243564.1, c.113G>A/p.R38H) in the DHDDS gene in the proband. Sanger sequencing further validated that the presence of the mutation in his affected mother but absent in the health family members. Further bioinformatics analysis revealed that this mutation (p.R38H), located in an evolutionarily conserved region of DHDDS, was predicted to be deleterious.Discussion: In this report, we present the first case of intractable epilepsy and/or myoclonus caused by p.R38H mutation of the DHDDS gene in the Chinese population. Furthermore, this study represents the third report of autosomal dominant familial inheritance of DHDDS mutation worldwide.https://www.frontiersin.org/articles/10.3389/fgene.2023.1208540/fullepilepsymyoclonusDHDDSmutationwhole exome sequencing |
| spellingShingle | Yi Dong Yi Zhang Yue Sheng Fang Wang Lv Liu Liang-Liang Fan Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonus Frontiers in Genetics epilepsy myoclonus DHDDS mutation whole exome sequencing |
| title | Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonus |
| title_full | Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonus |
| title_fullStr | Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonus |
| title_full_unstemmed | Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonus |
| title_short | Case report: Identification of a recurrent pathogenic DHDDS mutation in Chinese family with epilepsy, intellectual disability and myoclonus |
| title_sort | case report identification of a recurrent pathogenic dhdds mutation in chinese family with epilepsy intellectual disability and myoclonus |
| topic | epilepsy myoclonus DHDDS mutation whole exome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1208540/full |
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