Variance in the pathophysiological impact of the hemizygosity of gamma-aminobutyric acid type A receptor subunit genes between Prader-Willi syndrome and Angelman syndrome.

ABSTRACT

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.