A somatic mutation in MEN1 gene detected in periventricular nodular heterotopia tissue obtained from depth electrodes
| Autor: | Jay R. Gavvala, Alica M. Goldman, Zulfi Haneef, Robert Y. North, Daniel Yoshor, Terence Verla, Paul C. Van Ness, Janice Drabek, Laura Montier |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine MEN1 gene Pathology medicine.medical_specialty Candidate gene Tumor suppressor gene stereotactically placed EEG periventricular nodular heterotopia Brief Communication 03 medical and health sciences Epilepsy 0302 clinical medicine Germline mutation Proto-Oncogene Proteins hemic and lymphatic diseases Exome Sequencing medicine Humans MEN1 Multiple endocrine neoplasia Gene Exome business.industry Brain medicine.disease Electrodes Implanted 3. Good health somatic mosaicism 030104 developmental biology Neurology epilepsy Epilepsies Partial Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Epilepsia |
| ISSN: | 1528-1167 0013-9580 |
| DOI: | 10.1111/epi.16328 |
| Popis: | Periventricular nodular heterotopia (PNH) is a common structural malformation of cortical development. Mutations in the filamin A gene are frequent in familial cases with X‐linked PNH. However, many cases with sporadic PNH remain genetically unexplained. Although medically refractory epilepsy often brings attention to the underlying PNH, patients are often not candidates for surgical resection. This limits access to neuronal tissue harboring causal mutations. We evaluated a patient with PNH and medically refractory focal epilepsy who underwent a presurgical evaluation with stereotactically placed electroencephalographic (SEEG) depth electrodes. Following SEEG explantation, we collected trace tissue adherent to the electrodes and extracted the DNA. Whole‐exome sequencing performed in a Clinical Laboratory Improvement Amendments–approved genetic diagnostic laboratory uncovered a de novo heterozygous pathogenic variant in novel candidate PNH gene MEN1 (multiple endocrine neoplasia type 1; c.1546dupC, p.R516PfsX15). The variant was absent in an earlier exome profiling of the venous blood–derived DNA. The MEN1 gene encodes the ubiquitously expressed, nuclear scaffold protein menin, a known tumor suppressor gene with an established role in the regulation of transcription, proliferation, differentiation, and genomic integrity. Our study contributes a novel candidate gene in PNH generation and a novel practical approach that integrates electrophysiological and genetic explorations of epilepsy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text