Variance in the pathophysiological impact of the hemizygosity of gamma-aminobutyric acid type A receptor subunit genes between Prader-Willi syndrome and Angelman syndrome
| Autor: | Kiyoshi Egawa, Hideaki Shiraishi, Shinji Saitoh, Naoko Asahina |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Adolescent Hemizygosity Biology gamma-Aminobutyric acid 03 medical and health sciences Young Adult 0302 clinical medicine Developmental Neuroscience Internal medicine Angelman syndrome medicine UBE3A Humans Child Gene Loss function nutritional and metabolic diseases Chromosome Magnetoencephalography General Medicine Somatosensory Cortex medicine.disease Receptors GABA-A Electric Stimulation nervous system diseases Median Nerve Endocrinology Pediatrics Perinatology and Child Health Mutation GABAergic Female Neurology (clinical) Angelman Syndrome Prader-Willi Syndrome 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Braindevelopment. 43(4) |
| ISSN: | 1872-7131 |
| Popis: | Introduction Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are neurodevelopmental disorders caused by loss of function of maternally expressed UBE3A and paternally expressed contiguous genes on chromosome 15q11-13, respectively. A majority of these syndromes suffer from a large deletion of the relevant chromosome (AS Del or PWS Del), which includes biallelically expressed gamma-aminobutyric acid type A receptor subunit (GABAaR) genes, while remaining individuals present without the deletion (AS non-Del or PWS non-Del). We previously reported that AS Del, but not AS non-Del individuals, show aberrantly desynchronized somatosensory-evoked magnetic fields (SEFs) and speculated that it might reflect GABAergic dysfunction due to the hemizygosity of GABAaR genes. To verify its pathophysiological impact on PWS and AS, we analyzed the SEFs of PWS individuals. Method SEFs were recorded from eight PWS Del and two PWS non-Del individuals. The latency and strength of the first peak (N1m) were compared with those of AS Del/non-Del individuals and controls, most of which were obtained earlier. Results In contrast to AS, both PWS Del and PWS non-Del showed normal SEF waveforms. Desynchronized response with delayed N1m peak latency was exclusively indicated in AS Del. N1m strength was statistically higher in AS Del and AS non-Del, but not in PWS Del and PWS non-Del. Conclusions Our results indicate that the pathophysiological impact of the hemizygosity of GABAaR genes is lower in PWS than AS. UBE3A deficiency and the hemizygosity of GABAaR genes could synergistically deteriorate neuronal function, resulting in aberrant SEFs in AS Del. |
| Databáze: | OpenAIRE |
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