Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case report
Epilepsy is one of the most common neurological disorders affecting approximately 50 million people worldwide. It impacts people of all genders and ages, but evidence suggests a higher incidence rate in children and the elderly.Given that childhood epilepsy has the risk of causing developmental epil...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024175159 |
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| author | Sultan Makhmetov Kamila Temirkhanova Saule Rakhimova Nazerke Satvaldina Ruslan Kalendar Ulan Kozhamkulov Aidos Bolatov Mirgul Bayanova Assiya Bazenova Lyazzat Nazarova Ainur Akilzhanova Ulykbek Kairov |
| author_facet | Sultan Makhmetov Kamila Temirkhanova Saule Rakhimova Nazerke Satvaldina Ruslan Kalendar Ulan Kozhamkulov Aidos Bolatov Mirgul Bayanova Assiya Bazenova Lyazzat Nazarova Ainur Akilzhanova Ulykbek Kairov |
| author_sort | Sultan Makhmetov |
| collection | DOAJ |
| description | Epilepsy is one of the most common neurological disorders affecting approximately 50 million people worldwide. It impacts people of all genders and ages, but evidence suggests a higher incidence rate in children and the elderly.Given that childhood epilepsy has the risk of causing developmental epileptic encephalopathy, which is associated with intellectual, behavioral, and/or motor disabilities, proper assessment of children with new-onset epilepsy at an early stage is essential to prevent threats affecting neurodevelopmental processes. The aim of this study was to investigate whole genome sequencing data of children diagnosed with epilepsy. Our results revealed an identification of a novel mutation in a 2-year-old male patient who suffered from recurrent epileptic seizures of unknown etiology. The detected variant is heterozygous and located in gene CHRNA2 (chr8:27321348, NM_000742, c.612G > A, p.Trp204∗) in exon 6. The databases such as Varsome, GeneCards, and NCBI did not reveal any matches with previously identified variants, implying the novelty of the finding. Moreover, according to various prediction tools (MutationTaster, SIFT, CADD, FATHMM-MKL, LRT, DANN, Eigen, and BayesDel), the mutation is characterized as pathogenic, which corresponds to the American College of Medical Genetics and Genomics (ACMG) classification. According to the findings, mutation of the CHRNA2 gene is closely associated with two disorders known as autosomal dominant nocturnal frontal epilepsy (ADNFLE), and benign familial infantile epilepsy (BFIS). Comparison of proband's clinical manifestations showed that it is difficult to attribute precisely the patient's symptoms to either of the conditions, however the evidence suggests that the patient's symptoms are more consistent with those of ADNFLE. In this report, we expanded the spectrum of existing variations in the CHRNA2 gene contributing and associated with the development of epilepsy with the important and novel causative genetic variant. |
| format | Article |
| id | doaj-art-c383cb2afd4e457b8798cab85ba8bb06 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj-art-c383cb2afd4e457b8798cab85ba8bb062025-01-17T04:51:25ZengElsevierHeliyon2405-84402025-01-01111e41484Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case reportSultan Makhmetov0Kamila Temirkhanova1Saule Rakhimova2Nazerke Satvaldina3Ruslan Kalendar4Ulan Kozhamkulov5Aidos Bolatov6Mirgul Bayanova7Assiya Bazenova8Lyazzat Nazarova9Ainur Akilzhanova10Ulykbek Kairov11Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, KazakhstanCenter for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, KazakhstanCenter for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, KazakhstanCenter for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, KazakhstanCenter for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, KazakhstanCenter for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, KazakhstanUniversity Medical Center CF, Kerey-Zhanibek Khandar St. 5/1, 010000, Astana, KazakhstanUniversity Medical Center CF, Kerey-Zhanibek Khandar St. 5/1, 010000, Astana, KazakhstanUniversity Medical Center CF, Kerey-Zhanibek Khandar St. 5/1, 010000, Astana, KazakhstanUniversity Medical Center CF, Kerey-Zhanibek Khandar St. 5/1, 010000, Astana, KazakhstanCenter for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, KazakhstanCenter for Life Sciences, National Laboratory Astana, Nazarbayev University, Kabanbay Batyr Ave 53, Astana, 010000, Kazakhstan; Corresponding author.Epilepsy is one of the most common neurological disorders affecting approximately 50 million people worldwide. It impacts people of all genders and ages, but evidence suggests a higher incidence rate in children and the elderly.Given that childhood epilepsy has the risk of causing developmental epileptic encephalopathy, which is associated with intellectual, behavioral, and/or motor disabilities, proper assessment of children with new-onset epilepsy at an early stage is essential to prevent threats affecting neurodevelopmental processes. The aim of this study was to investigate whole genome sequencing data of children diagnosed with epilepsy. Our results revealed an identification of a novel mutation in a 2-year-old male patient who suffered from recurrent epileptic seizures of unknown etiology. The detected variant is heterozygous and located in gene CHRNA2 (chr8:27321348, NM_000742, c.612G > A, p.Trp204∗) in exon 6. The databases such as Varsome, GeneCards, and NCBI did not reveal any matches with previously identified variants, implying the novelty of the finding. Moreover, according to various prediction tools (MutationTaster, SIFT, CADD, FATHMM-MKL, LRT, DANN, Eigen, and BayesDel), the mutation is characterized as pathogenic, which corresponds to the American College of Medical Genetics and Genomics (ACMG) classification. According to the findings, mutation of the CHRNA2 gene is closely associated with two disorders known as autosomal dominant nocturnal frontal epilepsy (ADNFLE), and benign familial infantile epilepsy (BFIS). Comparison of proband's clinical manifestations showed that it is difficult to attribute precisely the patient's symptoms to either of the conditions, however the evidence suggests that the patient's symptoms are more consistent with those of ADNFLE. In this report, we expanded the spectrum of existing variations in the CHRNA2 gene contributing and associated with the development of epilepsy with the important and novel causative genetic variant.http://www.sciencedirect.com/science/article/pii/S2405844024175159EpilepsyInfantile seizuresAcetylcholine receptor alpha 2 subunitBenign familial infantile seizures (BFIS)Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) |
| spellingShingle | Sultan Makhmetov Kamila Temirkhanova Saule Rakhimova Nazerke Satvaldina Ruslan Kalendar Ulan Kozhamkulov Aidos Bolatov Mirgul Bayanova Assiya Bazenova Lyazzat Nazarova Ainur Akilzhanova Ulykbek Kairov Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case report Heliyon Epilepsy Infantile seizures Acetylcholine receptor alpha 2 subunit Benign familial infantile seizures (BFIS) Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) |
| title | Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case report |
| title_full | Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case report |
| title_fullStr | Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case report |
| title_full_unstemmed | Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case report |
| title_short | Novel nonsense mutation in gene CHRNA2 identified by whole-genome sequencing in infant with epilepsy disorder: A case report |
| title_sort | novel nonsense mutation in gene chrna2 identified by whole genome sequencing in infant with epilepsy disorder a case report |
| topic | Epilepsy Infantile seizures Acetylcholine receptor alpha 2 subunit Benign familial infantile seizures (BFIS) Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024175159 |
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