Research Archives - Page 60 of 60 - Yokohama City University

2018-01-26

Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy

Early-onset epileptic encephalopathies, includingWest syndrome (WS), are a group of neurological disorders characterized by developmental impairments and intractable seizures from early infancy. We have now identified biallelic CNPY3 variants in three individuals with WS; these include compound-heterozygous missense and frameshift variants in a family with two affected siblings (individuals 1 and 2) and a homozygous splicing variant in a consanguineous family (individual 3).

2018-01-16

Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits.

2018-01-04

Phosphorylation of an intrinsically disordered region of Ets1 shifts a multi-modal interaction ensemble to an auto-inhibitory state

Multi-modal interactions are frequently observed in intrinsically disordered regions (IDRs) of proteins upon binding to their partners. In many cases, post-translational modifications in IDRs are accompanied by coupled folding and binding. From both molecular simulations and biochemical experiments with mutational studies, we show that the IDR including a Ser rich region (SRR) of the transcription factor Ets1, just before the DNA-binding core domain, undergoes multi-modal interactions when the SRR is not phosphorylated.