2017
DOI: 10.1038/srep46227
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Unexplained Early Infantile Epileptic Encephalopathy in Han Chinese Children: Next-Generation Sequencing and Phenotype Enriching

Abstract: Early Infantile Epileptic Encephalopathy (EIEE) presents shortly after birth with frequent, severe seizures and progressive disturbance of cerebral function. This study was to investigate a cohort of Chinese children with unexplained EIEE, infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We used targeted next-generation sequencing to identify potential pathogenic variants of 308 genes in 68 Han Chinese patients with unexplained EIEE. A filter… Show more

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Cited by 31 publications
(31 citation statements)
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“…Ala1650Val variant has not been described before (#26), but has been seen several times with a threonine (Ala1650Thr) substitution in patients with severe DEE. 5,7,35 Arg1872Gln has also been seen several times in patients with severe DEE 7,36 ; however, we found it in a sib pair, with normal intellect and focal epilepsy (#34). The Gly1483Lys variant has previously been described in BFIS 17 ; the patient in this study (#18) carrying this variant has a very mild phenotype, with only speech delay, sporadic seizures, and discrete focal EEG abnormalities.…”
Section: Discussioncontrasting
confidence: 54%
“…Ala1650Val variant has not been described before (#26), but has been seen several times with a threonine (Ala1650Thr) substitution in patients with severe DEE. 5,7,35 Arg1872Gln has also been seen several times in patients with severe DEE 7,36 ; however, we found it in a sib pair, with normal intellect and focal epilepsy (#34). The Gly1483Lys variant has previously been described in BFIS 17 ; the patient in this study (#18) carrying this variant has a very mild phenotype, with only speech delay, sporadic seizures, and discrete focal EEG abnormalities.…”
Section: Discussioncontrasting
confidence: 54%
“…His presentation is more in keeping with an early onset (defined as less than 3 months) developmental and epileptic encephalopathy, as he did not have the burst‐suppression EEG signature of Ohtahara syndrome. All reported cases of pathogenic variants in ARX that lead to phenotypes of seizure onset prior to 3 months are captured in Table (Arafat et al, ; Bettella et al, ; Conti et al, ; Eksioglu et al, ; Fullston et al, ; Fullston et al, ; Giordano et al, ; Kato et al, ; Kwong et al, ; Sartori et al, ; Stromme et al, ; Tapie et al, ). Interestingly, several insertion variants in exon 5 of ARX that are predicted to cause altered or early termination of the ARX protein lead to severe and early onset epilepsy syndromes rather than the brain malformation/XLAG outcomes associated with complete loss‐of‐function variants (Table ).…”
Section: Discussionmentioning
confidence: 99%
“…Pathogenic variants within the homeodomain region are well characterized and generally abolish binding of ARX to target DNA sequences (Shoubridge, Tan, Seiboth, & Gecz, ). There are several variants, including insertion variants in exon 5 of ARX that are predicted to cause frameshift variants that are pathogenic, resulting in altered or early termination of the ARX protein, but not complete loss of function (Arafat et al, ; Bettella et al, ; Conti et al, ; Eksioglu, Pong, & Takeoka, ; Fullston et al, ; Fullston et al, ; Giordano et al, ; Kato, Koyama, Ohta, Miura, & Hayasaka, ; Kwong, Ho, Fung, & Wong, ; Sartori et al, ; Stromme et al, ; Tapie et al, ). These cases invariably lead to infantile onset developmental and epileptic encephalopathies such as Ohtahara Syndrome (also called early infantile epileptic encephalopathy) and West syndrome.…”
Section: Introductionmentioning
confidence: 99%
“…The study included 72 Chinese WS patients with no family history and with negative findings in the following: (i) metabolic, structural, immunological, and infectious etiologies (International League Against Epilepsy recommendations); (ii) chromosomal disorders (ie, Down's syndrome), copy number variation (CNV) diseases, and monogenic disorders (ie, Angelman syndrome or tuberous sclerosis complex); and (iii) Genetic‐structural modification of the brain (ie, tuberous sclerosis or DCX mutations leading to lissencephaly) . Peripheral blood samples were collected from patients and their parents via venipuncture …”
Section: Methodsmentioning
confidence: 99%