Additional file 1: Table S1. of SPATA5 mutations cause a distinct autosomal recessive phenotype of intellectual disability, hypotonia and hearing loss

Comparison of phenotypes of individuals with mutations in SPATA5. (DOCX 15 kb

Additional file 1: of Genome-wide rare copy number variation screening in ulcerative colitis identifies potential susceptibility loci

Supplementary material. (DOCX 7254 kb

Rare copy number variants in 517 patients with epilepsy.

<p>HS, hotspot region; Del, deletion; Dup, duplication; Inh, inherited; M, maternal; P, paternal;</p>∧<p>affected; -, parents unavailable; JME, juvenile myoclonic epilepsy; IAE, idiopathic absence epilepsy; CAE childhood absence epilepsy; IGE, idiopathic generalized epilepsy; GTCS, generalized tonic clonic seizures only; ID, intellectual disability; BECTS, benign epilepsy with centrotemporal spikes; IC, infantile convulsions; SIGEI, several idiopathic generalized epilepsy of infancy; NC, neonatal convulsions;</p><p>*two CNVs detected in same individual;</p><p>**15q13 deletions previously detected by MLPA <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000962#pgen.1000962-Helbig2" target="_blank">[60]</a>.</p

Two rare CNVs in five probands.

<p>Array CGH results are shown for the for two rare CNVs detected in probands EMJ071 (A), ND05260 (B), EPI51 (C), K034 (D), and EMJ117 (E). Array CGH results are depicted as in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000962#pgen-1000962-g001" target="_blank">Figure 1</a>; segmental duplications are not shown in this figure.</p

Gene-disrupting microdeletions found only in patients with genetic generalised epilepsy.

<p>GGE, genetic generalised epilepsy; CTR: population control; Chr: chromosome, start/end: genomic start and end point of the deleted segment, hg19; ^<i>P</i>-value: type-1 error rate for a χ2-test with df = 1; OR, 95%-CI, odds ratio with 95% confidence interval. Disease phenotype: ASD: autism spectrum disorder, ADHD: attention deficit hyperactivity disorder, AN: anorexia nervosa, AUT: autism, BPD: bipolar disorder, EE: epileptic encephalopathy, EPI: epilepsy, ID: intellectual disability, MCP: microcephaly, SCZ: schizophrenia; GGE syndromes: CAE: childhood absence epilepsy, JAE: juvenile absence epilepsy, JME: juvenile myoclonic epilepsy, EGMA: epilepsy with generalised tonic-clonic seizures alone predominantly on awakening, EGTCS: epilepsy with generalised tonic-clonic seizures alone, gsw: generalised spike and wave discharges on the electroencephalogram, number/: age-at-onset of afebrile generalised seizures. # previously published in [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005226#pgen.1005226.ref026" target="_blank">26</a>] and * [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005226#pgen.1005226.ref027" target="_blank">27</a>]. Bold gene symbols indicate genes previously implicated in epileptogenesis.</p><p>Gene-disrupting microdeletions found only in patients with genetic generalised epilepsy.</p

Functional gene enrichment and network analysis.

<p>Significant gene-set enrichments on 329 genes deleted in GGE patients revealed an enrichment of GRIN2B interacting proteins, genes of the MGI abnormal emotion/affect behaviour annotation and of the GO cognition annotation. Segmental clusters of genes belonging to a gene family were removed. Positional clustering of genes physically linked on a microdeletion is indicated by a slash between the gene symbols.</p><p>Functional gene enrichment and network analysis.</p

The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield

Objective: The Epilepsy Genetics Initiative (EGI) was formed in 2014 to create a centrally managed database of clinically generated exome sequence data. EGI performs systematic research-based reanalysis to identify new molecular diagnoses that were not possible at the time of initial sequencing and to aid in novel gene discovery. Herein we report on the efficacy of this approach 3 years after inception.Methods: One hundred sixty-six individuals with epilepsy who underwent diagnostic whole exome sequencing (WES) were enrolled, including 139 who had not received a genetic diagnosis. Sequence data were transferred to the EGI and periodically reevaluated on a research basis.Results: Eight new diagnoses were made as a result of updated annotations or the discovery of novel epilepsy genes after the initial diagnostic analysis was performed. In five additional cases, we provided new evidence to support or contradict the likelihood of variant pathogenicity reported by the laboratory. One novel epilepsy gene was discovered through dual interrogation of research and clinically generated WES.Significance: EGI's diagnosis rate of 5.8% represents a considerable increase in diagnostic yield and demonstrates the value of periodic reinterrogation of whole exome data. The initiative's contributions to gene discovery underscore the importance of data sharing and the value of collaborative enterprises.</p