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

• Published in: Clinical neurology and neurosurgery 2018-12, Vol.175, p.130-133
• Main Authors: Mateo-Montero, Raidili Cristina, Pedrera-Mazarro, Antonio, Martín-Palomeque, Guillermo, del Mar Moreno-Galera, María, Valera-Dávila, Carlos, Gómez-Ansede, Alicia, Braun, Jorge, Jiménez-Escrig, Adriano
• Format: Article
• Language: English
• Subjects: Behavior disorders; Calcium; Cell adhesion & migration; Deoxyribonucleic acid; DNA; Electrodes; Electromyography; Exome; Eye movements; Family medical history; Filtration; GABAergic interneurons; Gene expression; Genomes; Hereditary diseases; Interneurons; Magnetic resonance imaging; Musculoskeletal system; Mutation; Nervous system; Neurology; NMR; Nuclear magnetic resonance; Proteins; PVALB gene; REM sleep; REM sleep behaviour disorder; Sleep; Sleep disorders; Strain gauges; Synucleinopathy; γ-Aminobutyric acid
• ISSN: 0303-8467; 1872-6968
• DOI: 10.1016/j.clineuro.2018.09.035

•RBD idiopathic can have a genetic origin.•We report a kindred with a genetic form of REM behaviour disorder (RBD) with autosomal dominant transmission.•The PVALB is a calcium-binding albumin protein in gabaergic interneurons is inhibit the pyramidal cell during REM sleep.•The genetic study included exome sequencing disclosed PVALB gene most probably causing the phenotype. We report a kindred with a genetic form of REM behaviour disorder (RBD) with autosomal dominant transmission. 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. 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. 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.