Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi

De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies (CROSBI ID 211869)

Prilog u časopisu | stručni rad

Appenzeller, S ; ... ; Barišić, Nina ; ... ; Pal, Đorđe ; ... De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies // American journal of human genetics, 95 (2014), 4; 360-370

Podaci o odgovornosti

Appenzeller, S ; ... ; Barišić, Nina ; ... ; Pal, Đorđe ; ...

engleski

De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de novo mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction.

mutation; epileptic encephalopathies

EuroEPINOMICS-RES Consortium ; Epilepsy Phenome/Genome Project ; Epi4K Consortium.

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o izdanju

95 (4)

2014.

360-370

objavljeno

0002-9297

Povezanost rada

nije evidentirano

Indeksiranost