#617153
Table of Contents
A number sign (#) is used with this entry because of evidence that developmental and epileptic encephalopathy-45 (DEE45) is caused by heterozygous mutation in the GABRB1 gene (137190) on chromosome 4p13.
Developmental and epileptic encephalopathy-45 (DEE45) is a neurologic disorder characterized by global developmental delay apparent in infancy or early childhood and onset of seizures within the first 12 months of life. Affected individuals have severely impaired intellectual development, hypotonia, and other persistent neurologic deficits (summary by Burgess et al., 2019).
For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
The Epi4K Consortium and Epilepsy Phenome/Genome Project (2013) reported a 4.5-year-old boy with epileptic encephalopathy. The patient had onset of seizures at age 12 months and showed developmental regression at age 35 months. EEG showed hypsarrhythmia. He had global developmental delay, hypotonia, ataxia, cortical visual impairment, and thin corpus callosum.
Lien et al. (2016) reported a 32-month-old boy with severe developmental delay and hypotonia who developed refractory epilepsy at age 3 months. Brain imaging was normal.
Burgess et al. (2019) reported a 2-year-old girl (patient 63), born of unrelated parents of Italian and Moroccan origin, with DEE45. The patient had onset of focal and tonic seizures at 4 months of age with cessation of seizures at about 2 years of age. She had profoundly impaired intellectual development with hypotonia, dysmorphic features, and progressive cerebral and white matter atrophy on brain imaging. The patient was part of a large cohort of individuals with epilepsy of infancy with migrating focal seizures (EIMFS) who underwent genetic studies.
The heterozygous mutation in the GABRB1 gene that was identified in a patient with DEE45 by Burgess et al. (2019) occurred de novo.
In a boy with DEE45, the Epi4K Consortium and Epilepsy Phenome/Genome Project (2013) identified a de novo heterozygous missense mutation in the GABRB1 gene (F246S; 137190.0001). The patient was part of a cohort of 264 probands with epileptic encephalopathy who underwent exome sequencing. Functional studies of the variant were not performed. Janve et al. (2016) noted that the F246S mutation occurs at a highly conserved residue in transmembrane domain 1. In vitro functional studies in HEK293 cells showed that the mutation altered the kinetic properties of the channel, resulting in the net loss of GABAergic inhibition.
In a boy with DEE45, Lien et al. (2016) identified a de novo heterozygous missense mutation in the GABRB1 gene (T287I; 137190.0002). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variant were not performed.
In a 2-year-old girl (patient 63), born of unrelated parents of Italian and Moroccan origin, with DEE45, Burgess et al. (2019) identified a de novo heterozygous missense mutation in the GABRB1 gene (I247T; 137190.0003). The mutation, which was found by whole-exome sequencing, was not present in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed.
Burgess, R., Wang, S., McTague, A., Boysen, K. E., Yang, X., Zeng, Q., Myers, K. A., Rochtus, A., Trivisano, M., Gill, D., EIMFS Consortium, Sadleir, L. G., Specchio, N., Guerrini, R., Marini, C., Zhang, Y.-H., Mefford, H. C., Kurian, M. A., Poduri, A. H., Scheffer, I. E. The genetic landscape of epilepsy of infancy with migrating focal seizures. Ann. Neurol. 86: 821-831, 2019. Note: Erratum: Ann. Neurol. 87: 658 only, 2020. [PubMed: 31618474, related citations] [Full Text]
Epi4K Consortium and Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature 501: 217-221, 2013. [PubMed: 23934111, images, related citations] [Full Text]
Janve, V. S., Hernandez, C. C., Verdier, K. M., Hu, N., Macdonald, R. L. Epileptic encephalopathy de novo GABRB mutations impair gamma-aminobutyric acid type A receptor function. Ann. Neurol. 79: 806-825, 2016. [PubMed: 26950270, related citations] [Full Text]
Lien, E., Vatevik, A. K., Ostern, R., Haukanes, B. I., Houge, G. A second patient with a de novo GABRB1 mutation and epileptic encephalopathy. (Letter) Ann. Neurol. 80: 311-312, 2016. [PubMed: 27273810, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 442835; DO: 0080428; MONDO: 0014942;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p12 | Developmental and epileptic encephalopathy 45 | 617153 | Autosomal dominant | 3 | GABRB1 | 137190 |
A number sign (#) is used with this entry because of evidence that developmental and epileptic encephalopathy-45 (DEE45) is caused by heterozygous mutation in the GABRB1 gene (137190) on chromosome 4p13.
Developmental and epileptic encephalopathy-45 (DEE45) is a neurologic disorder characterized by global developmental delay apparent in infancy or early childhood and onset of seizures within the first 12 months of life. Affected individuals have severely impaired intellectual development, hypotonia, and other persistent neurologic deficits (summary by Burgess et al., 2019).
For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
The Epi4K Consortium and Epilepsy Phenome/Genome Project (2013) reported a 4.5-year-old boy with epileptic encephalopathy. The patient had onset of seizures at age 12 months and showed developmental regression at age 35 months. EEG showed hypsarrhythmia. He had global developmental delay, hypotonia, ataxia, cortical visual impairment, and thin corpus callosum.
Lien et al. (2016) reported a 32-month-old boy with severe developmental delay and hypotonia who developed refractory epilepsy at age 3 months. Brain imaging was normal.
Burgess et al. (2019) reported a 2-year-old girl (patient 63), born of unrelated parents of Italian and Moroccan origin, with DEE45. The patient had onset of focal and tonic seizures at 4 months of age with cessation of seizures at about 2 years of age. She had profoundly impaired intellectual development with hypotonia, dysmorphic features, and progressive cerebral and white matter atrophy on brain imaging. The patient was part of a large cohort of individuals with epilepsy of infancy with migrating focal seizures (EIMFS) who underwent genetic studies.
The heterozygous mutation in the GABRB1 gene that was identified in a patient with DEE45 by Burgess et al. (2019) occurred de novo.
In a boy with DEE45, the Epi4K Consortium and Epilepsy Phenome/Genome Project (2013) identified a de novo heterozygous missense mutation in the GABRB1 gene (F246S; 137190.0001). The patient was part of a cohort of 264 probands with epileptic encephalopathy who underwent exome sequencing. Functional studies of the variant were not performed. Janve et al. (2016) noted that the F246S mutation occurs at a highly conserved residue in transmembrane domain 1. In vitro functional studies in HEK293 cells showed that the mutation altered the kinetic properties of the channel, resulting in the net loss of GABAergic inhibition.
In a boy with DEE45, Lien et al. (2016) identified a de novo heterozygous missense mutation in the GABRB1 gene (T287I; 137190.0002). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variant were not performed.
In a 2-year-old girl (patient 63), born of unrelated parents of Italian and Moroccan origin, with DEE45, Burgess et al. (2019) identified a de novo heterozygous missense mutation in the GABRB1 gene (I247T; 137190.0003). The mutation, which was found by whole-exome sequencing, was not present in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed.
Burgess, R., Wang, S., McTague, A., Boysen, K. E., Yang, X., Zeng, Q., Myers, K. A., Rochtus, A., Trivisano, M., Gill, D., EIMFS Consortium, Sadleir, L. G., Specchio, N., Guerrini, R., Marini, C., Zhang, Y.-H., Mefford, H. C., Kurian, M. A., Poduri, A. H., Scheffer, I. E. The genetic landscape of epilepsy of infancy with migrating focal seizures. Ann. Neurol. 86: 821-831, 2019. Note: Erratum: Ann. Neurol. 87: 658 only, 2020. [PubMed: 31618474] [Full Text: https://doi.org/10.1002/ana.25619]
Epi4K Consortium and Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature 501: 217-221, 2013. [PubMed: 23934111] [Full Text: https://doi.org/10.1038/nature12439]
Janve, V. S., Hernandez, C. C., Verdier, K. M., Hu, N., Macdonald, R. L. Epileptic encephalopathy de novo GABRB mutations impair gamma-aminobutyric acid type A receptor function. Ann. Neurol. 79: 806-825, 2016. [PubMed: 26950270] [Full Text: https://doi.org/10.1002/ana.24631]
Lien, E., Vatevik, A. K., Ostern, R., Haukanes, B. I., Houge, G. A second patient with a de novo GABRB1 mutation and epileptic encephalopathy. (Letter) Ann. Neurol. 80: 311-312, 2016. [PubMed: 27273810] [Full Text: https://doi.org/10.1002/ana.24699]
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