Unraveling the diagnostic odyssey: stimulator of interferon gene-associated vasculopathy with onset in infancy in a 30-year-old female

Stimulator of interferon gene (STING)-associated vasculopathy with onset in infancy (SAVI) is an extremely rare autoinflammatory disease. We present the case of a female Korean patient with early-onset interstitial lung disease who was initially suspected to have systemic lupus erythematosus (SLE) but was ultimately diagnosed with SAVI. The patient exhibited signs of interstitial lung disease and cutaneous manifestations before the age of 1 year and continued to have recurrent fever accompanied by pulmonary infiltrates. Based on positive findings for antibodies associated with SLE, such as antinuclear antibodies and anti-double-stranded DNA, the pulmonary involvement was considered a manifestation of SLE. Another significant symptom was recurrent skin ulceration, which led to partial spontaneous amputation of most of the toes due to inflammation. Given the early onset of interstitial lung disease, severe skin ulcers, and symptoms resembling SLE, autoinflammatory syndrome, especially SAVI was suspected.Following confirmation by genetic testing at age 29 years, the patient was started on tofacitinib, a Janus kinase inhibitor. Despite the prolonged use of multiple immunosuppressive therapies, the patient’s lung condition continued to worsen, ultimately requiring lung transplantation. This observational report highlights the importance of considering SAVI as a potential diagnosis when manifestations of interstitial lung disease are observed during infancy. Early proactive treatment is crucial for lung involvement, as this can have long-term effects on patient’s prognosis.

Clinical applications of next-generation sequencing in the diagnosis of genetic disorders in Korea: a narrative review

Next-generation sequencing (NGS) technologies have revolutionized genetic testing and enabled efficient screening of various genetic conditions in clinical settings. However, the clinical application of genetic test results presents numerous significant challenges. This review aims to provide a comprehensive overview of key concepts for the clinical application of NGS, including (1) technical aspects and limitations, (2) variant classification, (3) clinical interpretation, (4) familial testing and genetic counseling, and (5) ethical considerations.Current Concepts: In short-read-based NGS, several limitations exist in detecting genomic variations, including repetitive sequences or complex structural variations. The variant classification process can be influenced by suspected genomic conditions and the accessibility of genomic databases. Therefore, the final genetic diagnosis depends on the physician’s discretion, which relies on the genotype-phenotype correlations and reverse phenotyping through additional evaluations. Familial testing can help trace the origin of variants and allele segregation and aid in variant interpretation, risk assessment, disease prevention, and family planning. In addition to addressing the clinical impact of genetic results, genetic counselors should also consider potential consequences related to ethical, legal, and social issues, including family dynamics.Discussion and Conclusion: NGS-based genetic testing is a promising diagnostic tool for genetic disorders, but proper variant interpretation and clinical evaluation are crucial for optimal clinical practice. Notably, ethical considerations and regulatory measures are required to prepare for the next era of genomic medicine.

Rapid Targeted Sequencing Using Dried Blood Spot Samples for Patients With Suspected Actionable Genetic Diseases

Background@#New genome sequencing technologies with enhanced diagnostic efficiency have emerged. Rapid and timely diagnosis of treatable rare genetic diseases can alter their medical management and clinical course. However, multiple factors, including ethical issues, must be considered. We designed a targeted sequencing platform to avoid ethical issues and reduce the turnaround time. @*Methods@#We designed an automated sequencing platform using dried blood spot samples and a NEOseq_ACTION panel comprising 254 genes associated with Mendelian diseases having curable or manageable treatment options. Retrospective validation was performed using data from 24 genetically and biochemically confirmed patients. Prospective validation was performed using data from 111 patients with suspected actionable genetic diseases. @*Results@#In prospective clinical validation, 13.5% patients presented with medically actionable diseases, including short- or medium-chain acyl-CoA dehydrogenase deficiencies (N=6), hyperphenylalaninemia (N=2), mucopolysaccharidosis type IVA (N=1), alpha thalassemia (N=1), 3-methylcrotonyl-CoA carboxylase 2 deficiency (N=1), propionic acidemia (N=1), glycogen storage disease, type IX(a) (N=1), congenital myasthenic syndrome (N=1), and citrullinemia, type II (N=1). Using the automated analytic pipeline, the turnaround time from blood collection to result reporting was <4 days. @*Conclusions@#This pilot study evaluated the possibility of rapid and timely diagnosis of treatable rare genetic diseases using a panel designed by a multidisciplinary team. The automated analytic pipeline maximized the clinical utility of rapid targeted sequencing for medically actionable genes, providing a strategy for appropriate and timely treatment of rare genetic diseases.

Clinical and molecular characteristics of Korean children with Cornelia de Lange syndrome

Purpose@#Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder caused by genetic variants of the cohesin complex. However, the diverse genetic etiologies and their phenotypic correlations in Korean patients with CdLS are still largely unknown. Hence, this study aimed to clarify the clinical characteristics and genetic background of Korean patients with CdLS. @*Materials and Methods@#The medical records of 15 unrelated patients (3 males and 12 females) genetically confirmed to have CdLS were retrospectively reviewed. All individuals were diagnosed with CdLS using target gene analysis, whole-exome sequencing, and/or chromosomal microarray analysis. The clinical score (CS) was calculated to assess disease severity. @*Results@#The median age at diagnosis was 1.7 (range, 0.0-11.8) years, and median follow-up duration was 3.8 (range, 0.4-11.7) years. Eight (53.3%) patients showed classic phenotypes of CdLS, two (13.3%) showed non-classic phenotypes, and five (33.3%) had other phenotypes sharing limited signs of CdLS. Fifteen causative variants were identified: NIPBL in five (33.3%, including 3 males), SMC1A in three (20.0%), SMC3 in three (20.0%), and HDAC8 in four (26.7%) patients. The CS was significantly higher in the NIPBL group than in the non-NIPBL group (14.2±1.3 vs. 8.7±2.9, P<0.001). @*Conclusion@#We identified the clinical and genetic heterogeneity of CdLS in Korean patients. Patients with variants of NIPBL had a more distinctive phenotype than those carrying variants of other cohesin complex genes (SMC1A, SMC3, and HDAC8). However, further studies are warranted to understand the pathogenesis of CdLS as a cohesinopathy and its genotype-phenotype correlations.

Abnormal Development of Neural Stem Cell Niche in the Dentate Gyrus of Menkes Disease

Background and Objectives@#Menkes disease (MNK) is a rare X-linked recessive disease, caused by mutations in the copper transporting ATP7A gene that is required for copper homeostasis. MNK patients experience various clinical symptoms including neurological defects that are closely related to the prognosis of MNK patients. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) produce new neurons throughout life, and defects in DG neurogenesis are often correlated with cognitive and behavioral problems. However, neurodevelopmental defects in the DG during postnatal period in MNK have not been understood yet. @*Methods@#and Results: Mottled-brindled (Mo Br/y ) mice (MNK mice) and littermate controls were used in this study. In vivo microCT imaging and immunohistochemistry results demonstrate that blood vasculatures in hippocampus are abnormally decreased in MNK mice. Furthermore, postnatal establishment of NSC population and their neurogenesis are severely compromised in the DG of MNK mice. In addition, in vitro analyses using hippocampal neurosphere culture followed by immunocytochemistry and immunoblotting suggest that neurogenesis from MNK NSCs is also significantly compromised, corresponding to defective neurogenic gene expression in MNK derived neurons. @*Conclusions@#Our study is the first reports demonstrating that improper expansion of the postnatal NSC population followed by significant reduction of neurogenesis may contribute to neurodevelopmental symptoms in MNK. In conclusion, our results provide new insight into early neurodevelopmental defects in MNK and emphasize the needs for early diagnosis and new therapeutic strategies in the postnatal central nerve system damage of MNK patients.

A case of TBC1D32-related ciliopathy with novel compound heterozygous variants

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

A case of TBC1D32-related ciliopathy with novel compound heterozygous variants

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

A Patient With Late-onset Limb-girdle Muscular Dystrophy Type 2B Mimicking Dermatomyositis: A Case Report and Review

Limb-Girdle Muscular Dystrophy 2B (LGMD2B) presents with proximal and/or distal muscle weakness and markedly high creatine kinase level. It is caused by the loss of dysferlin due to mutations in the DYSF gene. Due to its similar clinical features as inflammatory myopathy, it is often difficult to distinguish between the two. We present a case of a 48-year-old male who developed progressive proximal muscle weakness, papulosquamous lesions on the knuckles, elevated levels of muscle enzymes, and electromyogram abnormalities. Based on the clinical presentation, the initial impression was dermatomyositis, yet it was refractory to immunosuppressive therapy. Subsequently, dysferlin immunostaining and genetic analysis led to the final diagnosis of LGMD2B. This case shows that LGMD2B can present with extramuscular symptoms mimicking inflammatory myopathy in later stages of life. Dysferlin immunostaining and/or genetic analysis of the DYSF gene are essential for its diagnosis.

Clinical Spectrum of Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G-Associated Disease in Korean Children

Background@#and Purpose: The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOGantibody-positive demyelinating diseases in children. @*Methods@#This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. @*Results@#The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4–169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p= 0.011). @*Conclusions@#MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.

Shprintzen–Goldberg syndrome with a novel missense mutation of SKI in a 6-month-old boy

The Shprintzen–Goldberg syndrome (SGS) is an extremely rare genetic disorder caused by heterozygous variant in SKI . SGS is characterized by neurodevelopmental impairment with skeletal anomaly. Recognition of SGS is sometimes quite challenging in practice because it has diverse clinical features involving skeletal, neurological, and cardiovascular system. Here we report a case of a 6-month-old boy who initially presented with developmental delay and marfanoid facial features including prominent forehead, hypertelorism, high arched palate and retrognathia. He showed motor developmental delay since birth and could not control his head at the time of first evaluation. His height was above 2 standard deviation score. Arachnodactyly, hypermobility of joints, skin laxity, and pectus excavatum were also noted. Sequencing for FBN1 was negative, however, a novel missense variant, c.350G>A in SKI was identified by sequential whole exome sequencing. To our knowledge, this is the first case with SGS with phenotypic features of SGS overlapping with those of the Marfan syndrome, diagnosed by next generation sequencing in Korea.

Wide heterogeneity of congenital myasthenic syndromes: analysis of clinical experience in a tertiary center

Purpose@#Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of disorders characterized by impaired neuromuscular transmission. This study aims to provide the clue for early diagnosis and improved therapeutic strategies in CMS. @*Materials and Methods@#Through the targeted panel sequencing including twenty CMS causative genes, eleven patients were genetically confirmed and enrolled in this study. A retrospective medical record review was carried out for the clinical and laboratory data analysis. @*Results@#The age of patients ranged from 5 to 23 years, with the median age of 16 years. The peak age at onset of symptoms was the neonatal period. Seven out of the eleven patients were symptomatic at birth. The most commonly reported initial finding was generalized hypotonia with poor sucking and crying. Mean time to accurate diagnosis was 9.3±5.0 years. Total fifteen different variants in seven genes associated with CMS (DOK7, AGRN, RAPSN, CHRNE, COLQ, SLC5A7, and GFPT1) were identified. @*Conclusion@#We describe the clinical and genetic characteristics of CMS patients and treatment outcome in a single tertiary center. High clinical suspicion and timely molecular diagnosis is particularly important for the tailored therapy to maximize clinical improvement in CMS.

Erratum to: Elevated Serum Uric Acid in Benign Convulsions with Mild Gastroenteritis in Children

Unfortunately, the authors confirmed that some of the data was missing from categories ‘Acute gastroenteritis’ and ‘Febrile seizure’ of Table 2 in the original version.

Clinical and Genetic Spectrum of ATP1A3-Related Disorders in a Korean Pediatric Population

BACKGROUND@#AND PURPOSE: The aim of this study was to expand the understanding of the genotype-phenotype spectrum of ATP1A3-related disorders and to evaluate the therapeutic effect of a ketogenic diet in patients with alternating hemiplegia of childhood (AHC).@*METHODS@#The clinical information of 13 patients with ATP1A3 mutations was analyzed by performing retrospective chart reviews. Patients with the AHC phenotype who consented to ketogenic diet were included in the trial.@*RESULTS@#Ten patients presented with the clinical phenotype of AHC, two patients presented with rapid-onset dystonia parkinsonism, and one patient presented with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Two novel mutations of the AHC phenotype were identified: p.Ile363Thr and p.Asn743Ser. The clinical phenotypes of three mutations differed from those in previous reports: p.Arg597Pro, p.Thr769Pro, and p.Arg756Cys. One of the two patients who started a ketogenic diet experienced seizure provocation and so immediate stopped consuming the diet, while the other patient continued the ketogenic diet for 1 year, but this produced no clear benefit such as reduction of paroxysmal symptoms.@*CONCLUSIONS@#Our study is the first case series of ATP1A3-related disorders to be described in Korea and which further expands the understanding of its genotype-phenotype spectrum. A ketogenic diet showed no clear benefit for the patients with AHC.

Wide heterogeneity of congenital myasthenic syndromes: analysis of clinical experience in a tertiary center

Purpose@#Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of disorders characterized by impaired neuromuscular transmission. This study aims to provide the clue for early diagnosis and improved therapeutic strategies in CMS. @*Materials and Methods@#Through the targeted panel sequencing including twenty CMS causative genes, eleven patients were genetically confirmed and enrolled in this study. A retrospective medical record review was carried out for the clinical and laboratory data analysis. @*Results@#The age of patients ranged from 5 to 23 years, with the median age of 16 years. The peak age at onset of symptoms was the neonatal period. Seven out of the eleven patients were symptomatic at birth. The most commonly reported initial finding was generalized hypotonia with poor sucking and crying. Mean time to accurate diagnosis was 9.3±5.0 years. Total fifteen different variants in seven genes associated with CMS (DOK7, AGRN, RAPSN, CHRNE, COLQ, SLC5A7, and GFPT1) were identified. @*Conclusion@#We describe the clinical and genetic characteristics of CMS patients and treatment outcome in a single tertiary center. High clinical suspicion and timely molecular diagnosis is particularly important for the tailored therapy to maximize clinical improvement in CMS.

Association of Tumor Necrosis Factor-α Gene Promotor Variant, Not Interleukin-10, with Febrile Seizures and Genetic Epilepsy with Febrile Seizure Plus / 대한소아신경학회지

PURPOSE@#Cytokines demonstrate active roles in the occurrence of febrile seizures (FS). However, whether a genetic predisposition to inflammation is implicated in FS, febrile seizure plus (FS+) or genetic epilepsy with febrile seizure plus (GEFS+) are still unclear. Therefore we perform this study to find the association of promotor variants in pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) genes and anti-inflammatory cytokine interleukin 10 (IL-10) genes either with FS, FS+, and GEFS+ in Korean children.@*METHODS@#Fifty-seven children with FS, 32 FS+, and 12 GEFS+ patients were compared with 108 controls. The allelic and genotypic distributions were compared for TNF-α-238 (rs361525), −308 (rs1800629), −857 (rs1799724), −863 (rs1800630), and IL-10-592 (rs1800872), −819 (rs1800871), −1082 (rs1800896), and −1352 (rs1800893).@*RESULTS@#Allelic and genotypic frequencies of TNF-α and IL-10 promotor variants showed no significant differences between FS, FS+, and GEFS+ versus controls. However, AA genotypes at TNF-α-863 were present only in controls. TNF-α-863 (rs1800630) promoter variants showed an association with FS, FS+, and GEFS+ in a recessive mode of inheritance pattern (P<0.05).@*CONCLUSION@#Our results suggest that AA genotypes at TNF-α-863 may be associated with FS, FS+, and GEFS+, implicating protective roles against to development of FS, FS+, and GEFS+.

Erratum: Correction of Error in Result: Urological Problems in Patients with Menkes Disease

The authors regret that there was an important error in the results in Table 1; the ATP7A mutations detected in Patients 2 and 14 were incorrectly noted.

A familial case of limb-girdle muscular dystrophy with CAV3 mutation

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation.A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L).We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

Clinical and genetic characteristics of Korean patients with IARS2-related disorders

PURPOSE@#Genetic defects in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases were first identified as causes of various disorders in 2007. Variants in IARS2, which encodes a mitochondrial isoleucyl-tRNA synthetase, were first reported in 2014. These variants are associated with diverse phenotypes ranging from CAGSSS (CAtaracts, Growth hormone deficiency, Sensory neuropathy, Sensorineural hearing loss, and Skeletal dysplasia) and Leigh syndrome to isolated nonsyndromic cataracts. Here, we describe the phenotypic and genetic spectrum of Korean patients with IARS2-related disorders.@*MATERIALS AND METHODS@#Using whole-exome sequencing followed by Sanger sequencing, we identified five patients with IARS2 mutations. Their medical records and brain magnetic resonance images were reviewed retrospectively.@*RESULTS@#All five patients presented with developmental delay or regression before 18 months of age. Three patients had bilateral cataracts, but none had hearing loss or sensory neuropathy. No evidence of skeletal dysplasia was noted, but two had short stature. One patient had cardiomyopathy and another exhibited renal tubulopathy and hypoparathyroidism. Their brain imaging findings were consistent with Leigh syndrome. Interestingly, we found the recurrent mutations p.R817H and p.V105Dfs*7 in IARS2.@*CONCLUSION@#To our knowledge, this is the first report of Korean patients with IARS2-related disorders. Our findings broaden the phenotypic and genotypic spectrum of IARS2-related disorders in Korea and will help to increase clinical awareness of IARS2-related neurodegenerative diseases.

A Case of Familial Spondyloenchondrodysplasia with Immune Dysregulation Masquerading as Moyamoya Syndrome

No abstract available.

Association Analysis of Interleukin-1β, Interleukin-6, and HMGB1 Variants with Postictal Serum Cytokine Levels in Children with Febrile Seizure and Generalized Epilepsy with Febrile Seizure Plus

BACKGROUND AND PURPOSE: Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1β, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. METHODS: Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1β-31 (rs1143627), IL-1β-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1β, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. RESULTS: Near-complete linkage disequilibrium exists between IL-1β-31 and IL-1β-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1β levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1β-31 and IL-1β-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1β levels after AFS for CT genotypes of IL-1β-31 and IL-1β-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1. CONCLUSIONS: Genetic variants located in IL-1β-31 and IL-1β-511 promotor regions are correlated with higher postictal IL-1β levels in FS. These results suggest that IL-1 gene cluster variants in IL-1β-31 and IL-1β-511 are a host genetic factor for provoking FS in Korean children.