Clinical and genetical study of a familial form of REM sleep behavior disorder.

OBJECTIVE: We report a kindred with a genetic form of REM behaviour disorder (RBD) with autosomal dominant transmission. PATIENTS AND METHODS: Clinical, polysomnography study, genetic study and brain MRI were performed to evaluate the index patients. The genetic study included exome sequencing of the index cases that detected 60,869 variants in the individuals examined. RESULTS: The kindred has a RBD with autosomal dominant transmission starting in second decade of life. After filtering out the exome variants shared by two affected cases the pool of variants could be reduced to thirteen; one of them is in PVALB, a calcium-binding albumin protein present in gabaergic interneurons in the nervous system that inhibit the pyramidal cell during REM sleep. CONCLUSIONS: RBD can have a genetic origin. The results of the exome study in this kindred suggest that gabaergic circuits may be altered in patients with RBD. Further studies in this family or in other pedigrees with familial RBD may clear the role of this gene in this disorder.

RNA-Seq blood transcriptome profiling in familial attention deficit and hyperactivity disorder (ADHD).

We have carried an exploratory study by blood transcriptome to find RNA expression signatures in familial ADHD. Samples were collected from three cases with familial ADHD and their paired controls and evaluated by RNA-Seq. Transcriptome profiling identified 7 differentially expressed transcripts with a FDR <0.05 that were involved in pathways in Huntington's disease or axonal guidance signaling previously implicated in ADHD, and enriched for signal peptide, growth factor binding, and notably the lipid metabolism pathways. These findings show that blood transcriptome can have an associated signature and highlight a potential to use blood transcriptome to identify patterns of ADHD.