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Chromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population

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dc.contributor.authorTÜRKDOĞAN, DİLŞAD
dc.contributor.authorsTurkdogan, Dilsad; Turkyilmaz, Ayberk; Sager, Gunes; Ozturk, Gulten; Unver, Olcay; Say, Merve
dc.date.accessioned2022-03-12T22:55:02Z
dc.date.available2022-03-12T22:55:02Z
dc.description.abstractAim To identify genetic causes for early infantile epileptic encephalopathies (EIEE) in Turkish children with mostly consanguineous parents. Methods In a selected EIEE group (N = 59) based on results of nongenetic and initial genetic testing with unexplained etiology, 49 patients underwent array-based comparative genomic hybridization (aCGH) and 49 patients underwent whole exome sequencing (WES) including 39 with negative aCGH results and 10 with WES-only. Results Diagnostic yield of aCGH and WES for pathogenic or likely pathogenic variants was 14.3% and 38.8%, respectively. Including de novo variants of uncertain significance linked to compatible phenotypes, increased the diagnostic yield of WES to 61.2%. Out of 38 positive variants, 18 (47.4%) were novel and 16 (42.1%) were de novo. Twenty-one (56.8%) patients had recessive variants inherited from mostly consanguineous healthy parents (85.7%). Fourteen (37.8%) of patients with diagnostic results had positive variants in established EIEE genes. Seizures started during neonatal period in 32.4% patients. Posture or movement disorders were comorbid with EIEE in 40.5% of diagnosed patients. We identified treatable metabolic disorders in 8.1% of patients and pathogenic variants in genes which support using targeted medicine in 19% of patients. Conclusions Detailed electro-clinical phenotyping led to expansion of some of the known phenotypes with non-neurological and neurological findings in addition to seizures, as well as suggestion of candidate genes (SEC24B, SLC16A2 and PRICKLE2) and a copy number variant (microduplication of Xp21.1p11.4). The high ratio of recessive inheritance could be important for family counseling.
dc.identifier.doi10.1080/00207454.2021.1967349
dc.identifier.eissn1563-5279
dc.identifier.issn0020-7454
dc.identifier.pubmed34380004
dc.identifier.urihttps://hdl.handle.net/11424/236621
dc.identifier.wosWOS:000687599600001
dc.language.isoeng
dc.publisherTAYLOR & FRANCIS LTD
dc.relation.ispartofINTERNATIONAL JOURNAL OF NEUROSCIENCE
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectEarly infantile epileptic encephalopathies
dc.subjectchromosomal microarray
dc.subjectwhole exome sequencing
dc.subjectcandidate genes
dc.subjecttargeted therapy
dc.subjectrecessive inheritance
dc.subjectDE-NOVO MUTATIONS
dc.subjectGENETICS
dc.subjectEPILEPSIES
dc.subjectVARIANTS
dc.subjectSEIZURES
dc.subjectDELETION
dc.titleChromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population
dc.typearticle
dspace.entity.typePublication
local.avesis.id32ddc250-17fd-443f-917c-d7b3f852bb5b
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages18
oaire.citation.titleINTERNATIONAL JOURNAL OF NEUROSCIENCE
relation.isAuthorOfPublication0a1599c4-48ff-4aa9-b689-3927c986a650
relation.isAuthorOfPublication.latestForDiscovery0a1599c4-48ff-4aa9-b689-3927c986a650

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