Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsy
The KCNK4 gene, predominantly distributed in neurons, plays an essential role in controlling the resting membrane potential and regulating cellular excitability. Previously, only two variants were identified to be associated with human disease, facial dysmorphism, hypertrichosis, epilepsy, intellect...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1081097/full |
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| author | Hong-Jun Yan Yun-yan He Yun-yan He Liang Jin Liang Jin Qiang Guo Jing-Hua Zhou Sheng Luo Sheng Luo |
| author_facet | Hong-Jun Yan Yun-yan He Yun-yan He Liang Jin Liang Jin Qiang Guo Jing-Hua Zhou Sheng Luo Sheng Luo |
| author_sort | Hong-Jun Yan |
| collection | DOAJ |
| description | The KCNK4 gene, predominantly distributed in neurons, plays an essential role in controlling the resting membrane potential and regulating cellular excitability. Previously, only two variants were identified to be associated with human disease, facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth (FHEIG) syndrome. In this study, we performed trio-based whole exon sequencing (WES) in a cohort of patients with epilepsy. Two de novo likely pathogenic variants were identified in two unrelated cases with heterogeneous phenotypes, including one with Rolandic epilepsy and one with the FHEIG syndrome. The two variants were predicted to be damaged by the majority of in silico algorithms. These variants showed no allele frequencies in controls and presented statistically higher frequencies in the case cohort than that in controls. The FHEIG syndrome-related variants were all located in the region with vital functions in stabilizing the conductive conformation, while the Rolandic epilepsy-related variant was distributed in the area with less impact on the conductive conformation. This study expanded the genetic and phenotypic spectrum of KCNK4. Phenotypic variations of KCNK4 are potentially associated with the molecular sub-regional effects. Carbamazepine/oxcarbazepine and valproate may be effective antiepileptic drugs for patients with KCNK4 variants. |
| first_indexed | 2024-04-11T00:44:21Z |
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| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-11T00:44:21Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-1ff7ea5e5169431c80f6053823f190fb2023-01-05T19:39:05ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-01-011510.3389/fnmol.2022.10810971081097Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsyHong-Jun Yan0Yun-yan He1Yun-yan He2Liang Jin3Liang Jin4Qiang Guo5Jing-Hua Zhou6Sheng Luo7Sheng Luo8Epilepsy Center, Guangdong Brain Hospital, Guangzhou, ChinaInstitute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Neurology, Women and Children’s Hospital Affiliated to Qingdao University, Qingdao, ChinaInstitute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Neurology, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, ChinaEpilepsy Center, Guangdong Brain Hospital, Guangzhou, ChinaEpilepsy Center, Guangdong Brain Hospital, Guangzhou, ChinaEpilepsy Center, Guangdong Brain Hospital, Guangzhou, ChinaInstitute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe KCNK4 gene, predominantly distributed in neurons, plays an essential role in controlling the resting membrane potential and regulating cellular excitability. Previously, only two variants were identified to be associated with human disease, facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth (FHEIG) syndrome. In this study, we performed trio-based whole exon sequencing (WES) in a cohort of patients with epilepsy. Two de novo likely pathogenic variants were identified in two unrelated cases with heterogeneous phenotypes, including one with Rolandic epilepsy and one with the FHEIG syndrome. The two variants were predicted to be damaged by the majority of in silico algorithms. These variants showed no allele frequencies in controls and presented statistically higher frequencies in the case cohort than that in controls. The FHEIG syndrome-related variants were all located in the region with vital functions in stabilizing the conductive conformation, while the Rolandic epilepsy-related variant was distributed in the area with less impact on the conductive conformation. This study expanded the genetic and phenotypic spectrum of KCNK4. Phenotypic variations of KCNK4 are potentially associated with the molecular sub-regional effects. Carbamazepine/oxcarbazepine and valproate may be effective antiepileptic drugs for patients with KCNK4 variants.https://www.frontiersin.org/articles/10.3389/fnmol.2022.1081097/fullKCNK4FHEIG syndromerolandic epilepsymolecular sub-regional effectsphenotypic variations |
| spellingShingle | Hong-Jun Yan Yun-yan He Yun-yan He Liang Jin Liang Jin Qiang Guo Jing-Hua Zhou Sheng Luo Sheng Luo Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsy Frontiers in Molecular Neuroscience KCNK4 FHEIG syndrome rolandic epilepsy molecular sub-regional effects phenotypic variations |
| title | Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsy |
| title_full | Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsy |
| title_fullStr | Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsy |
| title_full_unstemmed | Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsy |
| title_short | Expanding the phenotypic spectrum of KCNK4: From syndromic neurodevelopmental disorder to rolandic epilepsy |
| title_sort | expanding the phenotypic spectrum of kcnk4 from syndromic neurodevelopmental disorder to rolandic epilepsy |
| topic | KCNK4 FHEIG syndrome rolandic epilepsy molecular sub-regional effects phenotypic variations |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1081097/full |
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