Papers of the week – Encephalitis-antibodies, FAN1, Art and Parent-of-Origin Effects

Dennis' paper of the week

Biggest surprise this week: Imprinted genes interact with non-imprinted genes frequently. But first sequencing reports, statistical frameworks for rare variants analyzes and an impressive translational result.

A novel encephalitis with seizures and the analysis of the effects of antibodies. In their study published in LANCET NEUROLOGY Petit-Pedrol and coworkers characterized serum and CSF samples for antigens in 140 patients with encephalitis, seizures or status epilepticus as well as antibodies to unknown neurophil antigens. High titres of serum and CSF GABAA receptor antibodies are reported to be associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both, which could be exploited for immunotherapy with 15 patients.

Art is a matter of taste. In a recent paper in Frontiers in NEUROSCIENCE Vessel and coworkers ask probands in fMRI scanners to rate different pieces of art. Their results suggest that a sense of being moved by certain artworks is specific to an individual’s unique neurological make-up, specifically the default mode network of the prefrontal cortex.

FAN1 in 15q13.3 CNVs. A team around Ionita-Laza exploited whole exomes sequencing data by a novel method for detection of rare variant clusters. Their statistical framework analyzes genomic regions affected by de novo copy number variants in association with disease. In their PNAS paper they propose that variants in the FAN1 gene are key drivers in the 15q13.3 locus for the associated psychiatric and neurodevelopmental phenotypes.

Clinical whole-genome sequencing in severe early-onset epilepsy. Martin et al. report in Hum. Mol. Genetics their Whole Genome Sequencing (WGS) results on six patients with severe early-onset epilepsy who had previously been refractory to molecular diagnosis. With identification of mutations in the strong epilepsy candidate genes SCN2A, KCNQ2, KCNT1, PIGQ and subsequent functional follow up, the study demonstrates the power WGS in a clinical setting.

Statistical test for small WES rare variant studies. Lee et al. extend in American Journal of Human Genetics paper the family of sequence kernel association tests (SKATs) with SKAT-O. A test that combines advantages of burden- and SKAT tests without losing power.

Parent-of-Origin Effects. It is generally accepted that imprinting of genes might play a role in etiology of complex diseases like epilepsy. Mott and colleagues demonstrate in a Cell paper by survey of 97 traits in mice that nonimprinted genes can generate parent-of-origin effects by interaction with imprinted loci. Looks like most quantitative trait loci in mice show parent-of-origin effects.