RGD Reference Report - The utility of exome sequencing for genetic diagnosis in a familial microcephaly epilepsy syndrome. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

The utility of exome sequencing for genetic diagnosis in a familial microcephaly epilepsy syndrome.

Authors: McDonell, LM  Warman Chardon, J  Schwartzentruber, J  Foster, D  Beaulieu, CL  Majewski, J  Bulman, DE  Boycott, KM  Boycott, KM 
Citation: McDonell LM, etal., BMC Neurol. 2014 Jan 31;14:22. doi: 10.1186/1471-2377-14-22.
RGD ID: 11541059
Pubmed: PMID:24479948   (View Abstract at PubMed)
PMCID: PMC3916514   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2377-14-22   (Journal Full-text)

BACKGROUND: Despite remarkable advances in genetic testing, many adults with syndromic epilepsy remain without a molecular diagnosis. The challenge in providing genetic testing for this patient population lies in the extensive genetic heterogeneity associated with epilepsy. Even for the subset of epilepsy patients that present with a defining feature, such as microcephaly, the number of possible genes that would require interrogation by Sanger sequencing is extensive and often prohibitively expensive. CASE PRESENTATION: We report a family of French Canadian descent with four adult children affected with severe intellectual disability, epilepsy and microcephaly born to consanguineous parents and evaluated by the Genetics Service to provide informed genetic counseling to unaffected family members regarding possible recurrence risks. We used whole-exome sequencing (WES) of DNA from one affected sibling as a first-line diagnostic tool and compared the prioritization of variants using two strategies: 1) focusing on genes with homozygous variants; and, 2) focusing on genes associated with microcephaly. Both approaches prioritized the same homozygous novel frameshift mutation (p.Arg608Serfs*26) in WDR62, a gene known to cause autosomal recessive primary microcephaly. Sanger sequencing confirmed the presence of the homozygous mutation in the other three affected siblings. CONCLUSIONS: WES and subsequent filtering of the rare variants in a single affected family member led to the rapid and cost-effective identification of a novel homozygous frameshift mutation in WDR62, thereby explaining the severe neurodevelopmental disorder in this family and facilitating genetic counseling. Our findings support WES as an effective first-line diagnostic tool in families presenting with rare genetically heterogeneous neurological disorders.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
intellectual disability  IAGP 11541059DNA:insertion:cds:c.1821dupT(p.R608Sfs*26)(human)RGD 
intellectual disability  ISOWDR62 (Homo sapiens)11541059; 11541059DNA:insertion:cds:c.1821dupT(p.R608Sfs*26)(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Wdr62  (WD repeat domain 62)

Genes (Mus musculus)
Wdr62  (WD repeat domain 62)

Genes (Homo sapiens)
WDR62  (WD repeat domain 62)


Additional Information