• Journal of Genetic Medicine
• /
• v.17 no.2
• /
• pp.92-96
• /
• 2020

Hypotonia, Ataxia, and Delayed Development Syndrome (HADDS) is an autosomal-dominant, extremely rare neurodevelopmental disorder caused by the heterozygous EBF3 gene mutation. EBF3 is located on chromosome 10q26.3 and acts as a transcription factor that regulates neurogenesis and differentiation. This syndrome is characterized by dysmorphism, cerebellar hypoplasia, urogenital anomaly, hypotonia, ataxia, intellectual deficit, and speech delay. The current report describes a 3-year-old Korean male carrying a de novo EBF3 mutation, c.589A>G (p.Asn197Asp), which was identified by whole exome sequencing. He manifested facial dysmorphism, hypotonia, strabismus, vermis hypoplasia, and urogenital anomalies, including vesicoureteral reflux, cryptorchidism, and areflexic bladder. This is the first report of a case of HADDS cause by an EBF3 mutation in the Korean population.

• Journal of IKEEE
• /
• v.24 no.4
• /
• pp.1109-1116
• /
• 2020

The matching score evaluating human copying ability can be a good measure to check children's developmental stages, or sports movements like golf swing and dance, etc. It also can be used as HCI for AR, VR applications. This paper presents a method to evaluate the motion similarity between demonstrator who initiates movement and participant who follows the demonstrator action. We present a quantification method of the similarity which utilizes Euclidean L2 distance of Openpose keypoins vector similarity. The proposed method adapts DTW, thus can flexibly cope with the time delayed motions.

• Journal of Animal Reproduction and Biotechnology
• /
• v.37 no.1
• /
• pp.48-54
• /
• 2022

Parthenogenesis is maternally uniparental reproduction through the embryonic development of oocytes without fertilization. Artificial activation of mature oocytes could generate homozygous haploid embryos with the extrusion of the second polar body. However, the haploid embryos showed low embryo development in preimplantation embryos. In this study, we investigated whether the electronic fusion of the haploid embryos could enhance embryo development and ESC establishment in mice. Haploid embryos showed the developmental delay from 4-cell to the blastocyst stage. The haploid blastomeres of the 2-cell stage were fused electronically, resulting in that the fused embryos showed a significantly higher rate of blastocysts compared to non-fused haploid embryos (55% vs. 37%). Further, the embryonic stem cells (ESCs) derived from the fused embryos were confirmed to be diploid. The rate of ESC establishment in fused embryos was significantly higher compared to non-fused ones. Based on the results, we concluded that the electronic fusion of haploid embryos could be efficient to generate homozygous ESCs.

• Journal of Korean Neurosurgical Society
• /
• v.65 no.6
• /
• pp.841-845
• /
• 2022

Objective : Chiari III malformations are extremely rare hindbrain malformations that are associated with a high early mortality rate, or severe neurologic deficits in the survivors. The treatment is early operative closure and cerebrospinal fluid diversion (CSF) shunting. Methods : We operated on 15 patients by repair and excision between July 2014 till June 2020 and retrospective data collection was done. Only one patient doesn't need ventriculoperitoneal (VP) shunt and the other 14 patients need a VP shunt. We described stepwise dissection and untethering of the cerebellum from the bony edge to regrowth and herniation of cerebellum again into this potential space and simple dural closure or repair with graft was done. Results : We started with VP in eight patients (53%) and the other seven patients (46.7%) started with excision and then six patients need VP shunt later on because four patients developed CSF leak and two patients developed increased high intracranial tension. Only four patients (26.7%) needed a blood transfusion. Conclusion : There are variations in the outcome and not all cases of Chiari malformation III will die and severe developmental delay is not a must. Proper management and repair carry a good prognosis.

• Genomics & Informatics
• /
• v.20 no.2
• /
• pp.24.1-24.8
• /
• 2022

Hypomyelinating leukodystrophy type 2 (HLD2), is an inherited genetic disease of the central nervous system caused by recessive mutations in the gap junction protein gamma 2 (GJC2/GJA12). HLD2 is characterized by nystagmus, developmental delay, motor impairments, ataxia, severe speech problem, and hypomyelination in the brain. The GJC2 sequence encodes connexin 47 protein (Cx47). Connexins are a group of membrane proteins that oligomerize to construct gap junctions protein. In the present study, a novel missense mutation gene c.760G>A (p.Val254Met) was identified in a patient with HLD2 by performing whole exome sequencing. Following the discovery of the new mutation in the proband, we used Sanger sequencing to analyze his affected sibling and parents. Sanger sequencing verified homozygosity of the mutation in the proband and his affected sibling. The autosomal recessive inheritance pattern was confirmed since Sanger sequencing revealed both healthy parents were heterozygous for the mutation. PolyPhen2, SIFT, PROVEAN, and CADD were used to evaluate the function prediction scores of detected mutations. Cx47 is essential for oligodendrocyte function, including adequate myelination and myelin maintenance in humans. Novel mutation p.Val254Met is located in the second extracellular domain of Cx47, both extracellular loops are highly conserved and probably induce intramolecular disulfide interactions. This novel mutation in the Cx47 gene causes oligodendrocyte dysfunction and HLD2 disorder.

• Clinical and Experimental Pediatrics
• /
• v.61 no.12
• /
• pp.403-406
• /
• 2018

Floating-Harbor syndrome is a rare autosomal dominant genetic disorder associated with SRCAP mutation. To date, approximately 50 cases of Floating-Harbor syndrome have been reported, but none have been reported in Korea yet. Floating-Harbor syndrome is characterized by delayed bony maturation, unique facial features, and language impairment. Here, we present a 6-year-old boy with a triangular face, deep-set protruding eyes, low-set ears, wide nose with narrow nasal bridge, short philtrum, long thin lips, clinodactyly, and developmental delay that was transferred to our pediatric clinic for genetic evaluation. He showed progressive delay in the area of language and cognition-adaption as he grew. He had previously undergone chromosomal analysis at another hospital due to his language delay, but his karyotype was normal. We performed targeted exome sequencing, considering several syndromes with similar phenotypes. Library preparation was performed with the TruSight One sequencing panel, which enriches the sample for about 4,800 genes of clinical relevance. Massively parallel sequencing was conducted with NextSeq. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the first Korean case of Floating-Harbor syndrome with a novel SRCAP (Snf2 related CREBBP activator protein) mutation (c.7732dupT, p.Ser2578Phefs*6), resulting in early termination of the protein; it was not found in either of his healthy parents or a control population. To our knowledge, this is the first study to describe a boy with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing in Korea.

• Clinical and Experimental Pediatrics
• /
• v.52 no.3
• /
• pp.289-294
• /
• 2009

Purpose : To assess the usefulness of magnetic resonance imaging (MRI), karyotyping, brainstem auditory evoked potential (BAEP), electroencephalogram (EEG), tandem mass screening test, and newborn metabolic screening test in children with language delay for diagnosing underlying diseases. Methods : From January 2000 to June 2007, a retrospective chart review was performed for 122 children with language delay who visited the Child Neurology Clinic at Yeungnam University Hospital and who underwent neuropsychologic tests and other diagnostic evaluations for underlying diseases. They were grouped into phenomenological diagnostic categories, and test results were analyzed according to the underlying diseases. Results : Of 122 patients, 47 (38.5%) had mental retardation, 40 (32.8%) had developmental language disorders, 23 (18.9 %) had borderline IQ, and 12 (9.8%) had autism spectrum disorder. In 26 (21.3%) cases, the causes or relevant clinical findings to explain language delay were found. Eight (10.4%) of 77 MRIs, 6 (8.0%) of 75 EEGs, and 4 (5%) of 80 BAEPs showed abnormal results. Results directly attributed to diagnosing underlying diseases were 2 hearing defects in BAEPs and 1 bilateral perisylvian cortical dysplasia in MRIs. No abnormal results were found in karyotyping, tandem mass screening tests, and new-born screening tests. Conclusion : Commonly used tests to diagnose the cause of language delay are not very effective and should only be used selectively, according to patient characteristics. However, despite the low diagnostic yields from these tests, because many patients show abnormal results, these tests are useful when conducted in complete evaluation.

• Korean Journal of Psychosomatic Medicine
• /
• v.24 no.2
• /
• pp.165-173
• /
• 2016

Objectives : Since the awareness of autism spectrum disorders(ASD) is growing, as a result, it is increasing numbers of infants and toddlers being referred to specialized clinics for a differential diagnosis and the importance of early autism spectrum disorders detection is emphasized. This study is to know the difference between ASD and intellectual disability(ID) from comparison of the demographics, clinical characters and obstetric complications. Methods : The participants are 816 toddlers who visited the developmental delay clinic(DDC) in National Health Insurance Ilsan hospital. The number of toddlers diagnosed as ASD and ID was 324 and 492. 75 toddlers out of 114 who returned to DDC were diagnosed as ID at the first visit but 7 of them had changed diagnosis to ASD at the second visit. After compared ASD with ID from the first visit, we analyzed characters of toddlers who had the changed diagnosis to ASD at the second visit. Results : As a result, the comparison between ASD and ID at the first visit shows that the boys have higher ratio, lower obstetric complication and lower language assessment score in ASD. The toddlers who had the changed diagnosis at the second visit were all boys and they had more cases of family history of developmental delay and had lower score of receptive language developmental quotient. Conclusions : These findings suggest that sex, language characteristics and obstetric complication could be useful in the early detection of ASD.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.17 no.1
• /
• pp.32-39
• /
• 2006

Objectives : The aim of this study was to examine the developmental and clinical characteristics associated with nocturnal enuresis in Korean children. Methods : Three hundred eighteen children with nocturnal enuresis, together with their parents, completed a parent questionnaire consisting of a Child Behavior Checklist(CBCL). Data related to the prenatal, perinatal and developmental history, past and current medical history were collected. Ninety-three normal students were selected as the control group. Results : The nocturnal enuresis group attained diurnal and nocturnal urinary control significantly later than those in the normal control group.49.2% of the children with nocturnal enuresis had the family history of nocturnal enuresis. Daytime incontinence was present in 41.3% of the nocturnal enuresis group. The percentages of sleep-related disturbances were significantly higher in the nocturnal enuresis group when compared to the normal control group.42.6% of the children with nocturnal enuresis experienced pharmacotherapy, and 0.4% experienced enuresis alarms. Conclusion : The results of this study suggest that children with nocturnal enuresis in Korea have a high genetic load and a possibility of developmental delay, which supports the neurodevelopmental point of view with regard to the etiology of nocturnal enuresis. The physicians in Korea prefer pharmacological interventions to alarm interventions in treating Korean children with nocturnal enuresis.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.14 no.1
• /
• pp.81-94
• /
• 2003

Objectives：Developmental reading disorder is a condition which manifests significant developmenttal delay in reading ability or persistent errors. About 3-7% of school-age children have this condition. The purpose of the present study was to validate the diagnostic values of Word/Nonword Reading Test and Letter-Symbol Discrimination Task for the purpose of overcoming the caveats of Basic Learning Skills Test. Methods：Sixty-three reading-disordered patients(mean age 10.48 years old) and sex, age-matched 77 normal children(mean age 10.33 years old) were selected by clinical evaluation and DSM-IV criteria. Reading I and II of Basic Learning Skills Test, Word/Nonword Reading Test, and Letter-Symbol Discrimination Task were carried out to them. Word/Nonword Reading Test：One hundred usual highfrequency words and one hundred meaningless nonwords were presented to the subjects within 1.2 and 2.4 seconds, respectively. Through these results, automatized phonological processing ability and conscious letter-sound matching ability were estimated. Letter-Symbol Discrimination Task：mirror image letters which reading-disordered patients are apt to confuse were used. Reliability, concurrent validity, construct validity, and discriminant validity tests were conducted. Results：Word/Nonword Reading Test：the reliability(alpha) was 0.96, and concurrent validity with Basic Learning Skills test was 0.94. The patients with developmental reading disorders differed significantly from normal children in Word/Nonword Reading Test performances. Through discriminant analysis, 83.0% of original cases were correctly classified by this test. Letter-Symbol Discrimination Task：the reliability(alpha) was 0.86, and concurrent validity with Basic Learning Skills test was 0.86. There were significant differences in scores between the patients and normal children. Factor analysis revealed that this test were composed of saccadic mirror image processing, global accuracy, mirror image processing deficit, static image processing, global vigilance deficit, and inattention-impulsivity factors. By discriminant analysis, 87.3% of the patients and normal children were correctly classified. Conclusion：The patients with developmental reading disorders had deficits in automatized visuallexical route, morpheme-phoneme conversion mechanism, and visual information processing. These deficits were reliably and validly evaluated by Word/Nonword Reading Test and Letter-Symbol Discrimination Task.