Levetiracetam-Induced Rhabdomyolysis Following Medication Re-Initiation.

Rhabdomyolysis is a potentially life-threatening condition in which skeletal muscle breaks down, resulting in the release of myoglobin and creatine kinase (CK) in the blood; CK accumulation can lead to kidney failure and death. Several case reports have reported incidences of levetiracetam (LEV)-induced rhabdomyolysis. However, there are currently no reports of new-onset rhabdomyolysis after restarting LEV in a patient who previously tolerated the medication with no side effects. In this report, we present the case of a 35-year-old male who developed rhabdomyolysis after being restarted on LEV following a generalized tonic-clonic seizure. The patient was loaded with LEV 1 g IV and subsequently restarted on LEV 500 mg PO BID immediately after admission, from which time his serum CK level began to steadily rise to a maximum of 47,078 U/L despite aggressive intravenous hydration. LEV was discontinued on day five of admission when it was suspected to be the cause of the elevated CK levels in the absence of other contributing factors. The patient's CK level decreased to 35,635 U/L on day six of admission and continued to decrease before reaching 5,556 U/L at discharge. It is important to closely monitor serum CK in patients initiating or restarting LEV. Other antiepileptic medications should be considered if CK levels remain persistently elevated without other inciting factors.

Epigenetic natural variation in Arabidopsis thaliana.

Cytosine methylation of repetitive sequences is widespread in plant genomes, occurring in both symmetric (CpG and CpNpG) as well as asymmetric sequence contexts. We used the methylation-dependent restriction enzyme McrBC to profile methylated DNA using tiling microarrays of Arabidopsis Chromosome 4 in two distinct ecotypes, Columbia and Landsberg erecta. We also used comparative genome hybridization to profile copy number polymorphisms. Repeated sequences and transposable elements (TEs), especially long terminal repeat retrotransposons, are densely methylated, but one third of genes also have low but detectable methylation in their transcribed regions. While TEs are almost always methylated, genic methylation is highly polymorphic, with half of all methylated genes being methylated in only one of the two ecotypes. A survey of loci in 96 Arabidopsis accessions revealed a similar degree of methylation polymorphism. Within-gene methylation is heritable, but is lost at a high frequency in segregating F(2) families. Promoter methylation is rare, and gene expression is not generally affected by differences in DNA methylation. Small interfering RNA are preferentially associated with methylated TEs, but not with methylated genes, indicating that most genic methylation is not guided by small interfering RNA. This may account for the instability of gene methylation, if occasional failure of maintenance methylation cannot be restored by other means.

Role of transposable elements in heterochromatin and epigenetic control.

Heterochromatin has been defined as deeply staining chromosomal material that remains condensed in interphase, whereas euchromatin undergoes de-condensation. Heterochromatin is found near centromeres and telomeres, but interstitial sites of heterochromatin (knobs) are common in plant genomes and were first described in maize. These regions are repetitive and late-replicating. In Drosophila, heterochromatin influences gene expression, a heterochromatin phenomenon called position effect variegation. Similarities between position effect variegation in Drosophila and gene silencing in maize mediated by "controlling elements" (that is, transposable elements) led in part to the proposal that heterochromatin is composed of transposable elements, and that such elements scattered throughout the genome might regulate development. Using microarray analysis, we show that heterochromatin in Arabidopsis is determined by transposable elements and related tandem repeats, under the control of the chromatin remodelling ATPase DDM1 (Decrease in DNA Methylation 1). Small interfering RNAs (siRNAs) correspond to these sequences, suggesting a role in guiding DDM1. We also show that transposable elements can regulate genes epigenetically, but only when inserted within or very close to them. This probably accounts for the regulation by DDM1 and the DNA methyltransferase MET1 of the euchromatic, imprinted gene FWA, as its promoter is provided by transposable-element-derived tandem repeats that are associated with siRNAs.