Our patients with SCARB2 mutations showed the clinical and neurophysiologic phenotype of PME, in which epilepsy could be extremely severe, extending the spectrum reported in the typical AMRF syndrome.
Action myoclonus renal failure (AMRF) syndrome is a rare form of progressive myoclonus epilepsy with renal dysfunction related to mutations in the SCARB2 gene.
In contrast to the reduced binding properties of the nonsense mutations, the only missense mutation (H363N) found in AMRF leads to increased binding of beta-GC to LIMP-2, indicating that this highly conserved histidine modifies the affinity of LIMP-2 to its ligand.
Mutations in the SCARB2 gene cause a rare autosomal recessive disease, progressive myoclonus epilepsy (PME) with or without renal failure, the former also being designated action myoclonus-renal failure syndrome.
With the present study, we demonstrate that disruption of the coiled-coil structure or AMRF disease-causing mutations abolish beta-GC binding, indicating the importance of an intact coiled-coil structure for the interaction of LIMP-2 and beta-GC.
With the present study, we demonstrate that disruption of the coiled-coil structure or AMRF disease-causing mutations abolish beta-GC binding, indicating the importance of an intact coiled-coil structure for the interaction of LIMP-2 and beta-GC.
To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features.
Progressive myoclonus epilepsy: extraneuronal brown pigment deposition and system neurodegeneration in the brains of Japanese patients with novel SCARB2 mutations.