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| Status |
Public on May 22, 2019 |
| Title |
Phenotypic cooperation of a KCNQ2 exon 7 partial duplication and compound copy number variations in genes associated to a severe epileptic and neurodevelopmental delay |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
A 6-year-old boy, second son of healthy parents affected with epileptic encephalopathy of neonatal onset. Pregnancy with gestational diabetes controlled with diet. Delivery was uneventful. Since 48 hours of life, he presented episodes of cyanosis, generalized hypertonia, and tonic asymmetric postures followed by apnea. Video-EEG at 5 days of life showed bilateral and asynchronous spike-and-wave. Seizures were refractory to phenobarbital but were controlled with phenytoin. Since 3 months of age, he presented with startle episodes without EEG correlate related to the wake and sleep transition together with dystonic postures. One month later, epileptic spasms without hypsarrhythmia were observed. No response to levetiracetam and valproic acid but stopped after lacosamide (LCS) treatment was initiated (11 months of age). Metabolic tests (including CSF studies), karyotype, and brain MRI were normal. Epileptic encephalopathy gene panel was negative including hyperekplexia related genes. Progressive increase of TSH was treated with oral L-t4. At 20 months he presented recurrence of spasms that were controlled with LCS dose adjustment. V-EEG: abnormal background activity and paroxysmal multifocal discharges that showed activation and generalization during sleep. After several years of good seizure control, LCS was discontinued. He suffered from decompensation of seizures with febrile viral infection and at 5 years of age he presented startle episodes associated to auditory stimulus without EEG correlate, but during sleep, he presented epileptic spasms with EEG correlate. Treatment with vigabatrine was initiated with a clinical and EEG improvement. At physical exam he presents severe axial hypotonia without head control. Hypertonia of 4 limbs with dystonic movements of upper limbs. No hand use and is not able to sit or crawl. No development of expressive language.GMFCS: V. No development of expressive language. Last v-EEG monitoring showed bilateral polyspike discharges and clinical spasms in polygraph recording without any clear EEG correlate. Whole exome sequencing was performed and partial exon 7 duplication, heterozygous variant, in KCNQ2 was found. aCGH study detected several CNV in genes associated to neural functions (losses: LRRC55, PCDH9, NALCN, RYR3, ELAVL2, CDH13, ATP1A2, SLC17A5, ANO3. Gains : PCDH19, TENM1, EFNA5).
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| Overall design |
A high-density CytoScan® HD Array (Thermo Fisher Scientific, In), which includes 2.67 million markers for copy number (CN) analysis, 750,000 SNP probes and 1.9 million non-polymorphic probes for comprehensive whole-genome coverage was used. Following hybridization, the laser scanner (GeneChip® 3000 Scanner) was used for scanning the arrays, and the images were extracted and analyzed using Affymetrix Gene Chip Command Console software (version 4.0) and Chromosome analysis software (ChAS v.1.2/na33.2) (Fisher Scientific, Inc.), and interpreted with the aid of the UCSC genome browser.
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| Contributor(s) |
Lazo PA, García-Hernández JL, Gómez-Puertas P, Marcos-Alcalde I, Arjona C, Villarroel A, González-Sarmiento R, Fons C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 15, 2018 |
| Last update date |
May 25, 2019 |
| Contact name |
Juan Luis Garcia |
| E-mail(s) |
jlgarcia@usal.es
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| Phone |
+34923294812
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| Organization name |
Centro de Investigación del Cáncer IBMCC-CIC
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| Lab |
Laboratorio 12
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| Street address |
Campus Miguel de Unamuno
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| City |
Salamanca |
| State/province |
Salamanca |
| ZIP/Postal code |
37007 |
| Country |
Spain |
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| Platforms (1) |
| GPL16131 |
[CytoScanHD_Array] Affymetrix CytoScan HD Array |
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| Samples (4)
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| GSM3475295 |
Peripheral_blood_Affected_Son_Epileptic_Encephalopathy |
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| Relations |
| BioProject |
PRJNA505669 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122584_RAW.tar |
499.5 Mb |
(http)(custom) |
TAR (of CEL, CYCHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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