• 생명과학회지
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• 제33권5호
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• pp.429-435
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• 2023

역학 연구에 따르면 임신 중 산모의 감염, 산모의 스트레스, 환경적 위험 요인이 태아의 인지 장애와 관련된 뇌 발달 이상 위험을 증가시키고 정신분열증 및 자폐 스펙트럼 장애에 대한 감수성을 증가시키는 것으로 나타났다. 여러 동물 모델은 모체 면역 활성화(MIA)가 태아와 자손의 비정상적인 뇌 발달 및 행동 결함을 유발하기에 충분하다는 것이 입증되었다. 모체 면역활성화 동물 모델에는 흔히 바이러스 모방 Poly I:C 또는 박테리아 유래물질 LPS 등을 임신한 어미에 도입시킴으로서 모체 면역이 활성화되며, 친염증성 사이토카인이 증가하고 자손의 뇌에서 미세아교세포 활성이 관찰되었다. 미세아교세포는 중추신경계에서 중재 역할을 하는 뇌 상주 면역 세포이다. 미세아교세포는 식균 작용, 시냅스 형성 및 분지, 혈관 신생과 같은 다양한 기능을 담당하는 것으로 알려져 있다. 여러 연구에서 미세아교세포가 모체면역활성화 자손에서 활성화되어 있고, 다양한 사이토카인과의 상호작용을 통해 자손 행동에 영향을 미침이 보고되었다. 또한 신경세포와 별아교세포와의 상호작용을 통해 뇌회로에서도 중요한 역할을 담당한다. 그러나 미세아교세포가 뇌 발달 및 행동 결함에 필수적인지에 대해서는 논란이 있으며 정확한 메커니즘은 아직 알려지지 않다. 따라서 뇌 발달 장애의 잠재적 진단 및 치료를 위해서는 모체면역활성화 동물 모델에서 미세아교세포 기능 연구의 필요성이 더욱 요구되고 있다.

• 생물정신의학
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• 제4권1호
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• pp.74-83
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• 1997

With increasing tendency of incidence and interest for the late onset schzophrenia, concerns about whether this disorder is etiologically or phenomenogically distinctive entity or not have increased also. To clarify the disease entity of the late onset schzophrenia and the role of structural brain changes in its etiology, authors tried to prove following hypothesis : Are there any evidences of structural brain changes in the lateonset schizophrenia? ; If present, are they not different from those of the early-onset schizophrenia or progressive schizophrenia? ; And are they not different from those of senile dementia? Subjects were 6 patients with the late-onset schizophrenia, 6 patients with the early-onset schizophrenia, 6 patients with progressive schizophrenia, 6 patients with Alzheimer's dementia, and 6 controls. We measured regions of interest of the magnetic resonance images by computer assisted planimetry using the AutoCad and digitizer. Our study results may suggest that the third ventricular enlargement and a reversal of normal difference between left and right temporal lobe and left-right difference in posterior lateral ventricle are common brain pathology for all types of schizophrenia including the late onset schzophrenia. And also suggest that brain structural changes of the late onset schizophrenia are related with neurodevelopmental abnormality rather than degenerative change.

• Clinical and Experimental Pediatrics
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• 제45권4호
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• pp.540-544
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• 2002

저자들은 임상적으로 Rett 증후군이 의심된 2세 환아에서 MECP2 유전자의 직접 염기 서열 분석을 통해 P152R 돌연변이를 확인하였다. 이에 대한 문헌 고찰과 함께 보고하는 바이다.

• Clinical and Experimental Pediatrics
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• 제63권6호
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• pp.219-225
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• 2020

Background: There is increasing concern that moderate preterm (32-33 weeks' gestation) and late preterm (34-36 weeks' gestation) birth may be associated with minor neurodevelopmental problems affecting poor school performance. Purpose: We explored the cognitive function, cognitive visual function, executive function, and behavioral problems at school age in moderate to late preterm infants. Methods: Children aged 7-10 years who were born at 32⁺⁰ to 36⁺⁶ weeks of gestation and admitted to the neonatal intensive care unit from August 2006 to July 2011 at the National Health Insurance Service Ilsan Hospital were included. We excluded children with severe neurologic impairments, congenital malformations, or chromosomal abnormalities. Neuropsychological assessments consisted of 5 neuropsychological tests and 3 questionnaires. Results: A total of 37 children (mean age, 9.1±1.2 years) participated. The mean gestational age at birth was 34.6±7.5 weeks, while the mean birth weight was 2,229.2±472.8 g. The mean full-scale intelligence quotient was 92.89±11.90; 24.3% scored between 70 and 85 (borderline intelligence functioning). An abnormal score was noted for at least one of the variables on the attention deficit hyperactivity disorder diagnostic system for 65% of the children. Scores below borderline function for executive quotient and memory quotient were 32.4% and 24.3%, respectively. Borderline or clinically relevant internalizing problems were noted in 13.5% on the Child Behavior Check List. There were no significant associations between perinatal factors or socioeconomic status and cognitive, visual perception, executive function, or behavior outcomes. Conclusion: Moderate to late preterm infants are at risk of developing borderline intelligence functioning and attention problems at early school age. Cognitive and executive functions that are important for academic performance must be carefully monitored and continuously followed up in moderate to late preterm infants.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제30권1호
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• pp.34-41
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• 2019

Objectives: We aimed to compare preterm, neurodevelopmentally disordered and healthy full-term children. Methods: We enrolled 47 children who were born preterm, 40 neurodevelopmentally disordered children, and 80 healthy children as control participants, in order to assess the cognitive functioning and the risk of behavioral problems at the age of 5. Children were assessed using the Korean Wechsler Preschool and Primary Scale of Intelligence-4th edition (K-WPPSI-IV), the Child Behavior Checklist (CBCL), and the Temperament and Character Inventory (TCI). Results: The mean K-WPPSI-IV score of the preterm group was $87.19{\pm}17.36$, which was significantly higher than that of the neurodevelopmental disorder group ($69.98{\pm}28.63$; p<0.001) but lower than that of the control group ($107.74{\pm}14.21$; p<0.001). The cumulative CBCL scores of the preterm children were not significantly different from those of the control group. Additionally, the TCI scores for reward dependence of the preterm children were higher than those of the control group. Conclusion: The cognitive performance of preterm infants was lower than that of healthy full-term infants at the age of 5, and there was an association between slower growth and decreased cognitive ability.

• Genomics & Informatics
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• 제19권4호
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• pp.44.1-44.9
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• 2021

Autism is a complex neurodevelopmental disorder, the prevalence of which has increased drastically in India in recent years. Neuroligin is a type I transmembrane protein that plays a crucial role in synaptogenesis. Alterations in synaptic genes are most commonly implicated in autism and other cognitive disorders. The present study investigated the neuroligin 3 gene in the Indian autistic population by sequencing and in silico pathogenicity prediction of molecular changes. In total, 108 clinically described individuals with autism were included from the North Karnataka region of India, along with 150 age-, sex-, and ethnicity-matched healthy controls. Genomic DNA was extracted from peripheral blood, and exonic regions were sequenced. The functional and structural effects of variants of the neuroligin 3 protein were predicted. One coding sequence variant (a missense variant) and four non-coding variants (two 5'-untranslated region [UTR] variants and two 3'-UTR variants) were recorded. The novel missense variant was found in 25% of the autistic population. The C/C genotype of c.551T>C was significantly more common in autistic children than in controls (p = 0.001), and a significantly increased risk of autism (24.7-fold) was associated with this genotype (p = 0.001). The missense variant showed pathogenic effects and high evolutionary conservation over the functions of the neuroligin 3 protein. In the present study, we reported a novel missense variant, V184A, which causes abnormal neuroligin 3 and was found with high frequency in the Indian autistic population. Therefore, neuroligin is a candidate gene for future molecular investigations and functional analysis in the Indian autistic population.

• Journal of Genetic Medicine
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• 제21권1호
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• pp.31-35
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• 2024

Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked neurodevelopmental disorder with abnormal thyroid function caused by mutation in the solute carrier family 16 member 2 (SLC16A2) gene. Clinical manifestations of AHDS are global or axial hypotonia, a variety of movement disorders, severe intellectual disability, quadriplegia or spastic diplegia, growth failure, and seizures. A 10-year-old boy visited our hospital with the chief complaint of newly onset generalized tonic seizures with vocalization of weekly to daily frequency. He showed early infantile hypotonia, severe intellectual disability, and frequent respiratory infections. He could not walk independently and was non-verbal. Electroencephalogram revealed generalized slow spike and waves with multifocal spikes and slow background rhythms. His tonic seizures were controlled with more than two anti-seizure medications (ASMs). At 11 years of age, he was evaluated for thyroid function as part of regular screening for ASM maintenance and was found to have abnormal thyroid function. We performed whole exome sequencing for severe global developmental delay, drug-resistant epilepsy, and abnormal thyroid function. The hemizygous c.940C>T (p.Arg314Ter) variant in the SLC16A2 gene (NM_006517.5) was identified and confirmed based on Sanger sequencing. Herein, we describe a case of an AHDS patient with late-onset drug-resistant epilepsy combined with congenital hypotonia, global developmental delay, and abnormal thyroid function results. To the best of our knowledge, this is the oldest adolescent among AHDS cases reported in Korea. In this report, clinical characteristics of a mid-adolescence patient with AHDS were presented.

• 대한장애인치과학회지
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• 제13권2호
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• pp.80-85
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• 2017

저자는 불량한 구강 위생과 다수 치아에 광범위한 치아 우식증을 보이나 치과 검진과 치료에 협조가 되지 않는 엔젤만 증후군 환자를 전신마취 하에 안전하고 효과적으로 치료한 증례를 보고하는 바이다. 환아는 간질 조절을 위해 항경련제(Clobazam)를 복약 중이었고 운동 장애, 발육 지연, 언어 장애, 불수의적 폐구 운동을 보였다. GABA 수용체 이상이 동반되는 AS의 특성 상 진정 약물의 효과가 떨어질 수 있으며, 발작 가능성이 있기 때문에 전신마취를 행동조절 요법으로 선택하였고, 모든 생징후를 안전하게 감시하며 성공적으로 치과 치과치료를 시행하였다. 전신마취 이후에는 정기검진, 비약물적 행동조절 요법을 통해 간단한 수복 치료를 추가로 시행할 수 있었고, 환자의 구강 건강 증진에 기여할 수 있었다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제18권2호
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• pp.123-129
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• 2007

Objectives: Autism is a complex neurodevelopmental spectrum disorder with a strong genetic component. Previous neurochemical and genetic studies have suggested the possible involvement of the serotonin system in autism. Tryptophan 2,3-dioxygenase(TDO2) is the rate-limiting enzyme in the catabolism of tryptophan, which is the precursor of serotonin synthesis. The aim of this study was to investigate the association between the TDO2 gene and autism spectrum disorders(ASD) in a Korean population. Methods: The patients were diagnosed with ASD on the basis of the DSM-IV diagnostic classification outlined in the Korean version of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The present study included the detection of four single nucleotide polymorphisms(SNPs) in the TDO2 gene(rs2292536, rs6856558, rs6830072, rs6830800) and the family-based association analysis of the single nucleotide polymorphisms in Korean ASD trios using a transmission disequilibrium test(TDT) and haplotype analysis. The family trios of 136 probands were included in analysis. 87.5% were male and 86.0% were diagnosed with autism. The mean age of the probands was $78.5{\pm}35.8$ months(range: 26-264 months). Results: Two SNPs showed no polymorphism, and there was no significant difference in transmission in the other two SNPs. We also could not find any significant transmission in the haplotype analysis(p>.05). Conclusion: We could not find any significant statistical association between the transmission of SNPs in the TDO2 gene and ASD in a Korean population. This result may not support the possible involvement of the TDO2 gene in the development of ASD, and further exploration might be needed to investigate other plausible SNP sites.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제21권1호
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• pp.17-22
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• 2010

Objectives ： Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by abnormalities of social functioning, communication and behavior. The association of the 7q21-34 region with ASD has been reported. The DLX6 gene, which is located at the 7q22 region, is one of the positional and functional candidate genes for ASD. We found that there is no association between DLX6 polymorphisms and ASD in the Korean male population. Methods ： We selected three single nucleotide polymorphisms (SNPs) that might be implicated in the change of the DLX6 gene expression. The genomic DNA was collected from the venous blood of 147 male controls and 179 male patients with ASD. The genotypes of the selected SNPs were determined using the Illumina GoldenGate assay, and the statistical analyses were performed using HapAnalyzer software and SAS Enterprise. Results ： We found no association of the three SNPs in the DLX6 gene with ASD in the Korean male population. Conclusion ： Our study suggests that the three SNPs in the DLX6 gene are not associated with ASD, and we need to analyze the previously reported regions for their associations with ASD.