• Journal of Genetic Medicine
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• v.5 no.1
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• pp.15-20
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• 2008

Purpose : Large exon deletions in the DMD gene are found in about 60% of DMD/BMD patients. Multiplex PCR has been employed to detect the deletion mutation, which frequently generates noise PCR products due to the presence of multiple primers in a single reaction as well as the stringency of PCR conditions. This often leads to a false-negative or false-positive result. To address this problematic issue, we introduced the dual primer oligonucleotide (DPO) system. DPO contains two separate priming regions joined by a polydeoxyinosine linker that results in high PCR specificity even under suboptimal PCR conditions. Methods : We tested 50 healthy male controls, 50 patients with deletion mutation as deletion-positive patient controls, and 20 patients with no deletions as deletion-negative patient controls using DPO-multiplex PCR. Both the presence and extent of deletion were verified by simplex PCR spanning the promoter region (PM) and 18 exons including exons 3, 4, 6, 8, 12, 13, 17, 19, 43-48, 50-52, and 60 in all 120 controls. Results : DPO-multiplex PCR showed 100% sensitivity and specificity for the detection a deletion. However, it showed 97.1% sensitivity and 100% specificity for determining the extent of deletions. Conclusion : The DPO-multiplex PCR method is a useful molecular test to detect large deletions of DMD for the diagnosis of patients with DMD/BMD because it is easy to perform, fast, and cost-effective and has excellent sensitivity and specificity.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.103-108
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• 2017

Kabuki syndrome is a rare congenital disorder that causes multiple birth defects and mental retardation. Mutation of the lysine methyltransferase 2D (KMT2D) gene is the primary cause of Kabuki syndrome. We report a 4-year-old Korean girl diagnosed with Kabuki syndrome based on distinctive facial features (eversion of the lower lateral eyelid, arched eyebrows, depressed nasal tip, prominent ears), skeletal anomalies, short stature, and molecular analysis, which revealed a novel frameshift mutation in the KMT2D gene. A 4-year-old patient had a past history of congenital cardiac malformations (coarctation of the aorta, ventricular septal defect, atrial septal defect, patent ductus arteriosus), subclinical hypothyroidism and dysmorphic features at birth including webbed neck, short fingers, high arched palate, micrognathia and horseshoe kidney. She showed unique facial features such as a long palpebral fissure, long eyelashes, arched eyebrows with sparseness of the lateral third, broad nasal root, anteverted ears, and small mouth. Her facial features suggested Kabuki syndrome, and genetic analysis discovered a novel heterozygous frameshift mutation (c.4379dup, p.Leu1461Thrfs*30) in exon 15 of the KMT2D gene. The diagnosis of our 4-year-old patient was made through thorough physical examination and history taking, and genetic testing. It is challenging to diagnose patients with Kabuki syndrome at birth, since the characteristic facial features are expressed gradually during growth. Clinical suspicion aroused by regular follow-ups may lead to earlier diagnosis and interventions.

• Journal of Genetic Medicine
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• v.8 no.1
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• pp.71-75
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• 2011

A male infant was diagnosed with obstetric brachial plexus injury, congenital muscular torticollis and cleft palate 17 days after birth. His mother presented with gestational diabetes and premature rupture of membranes. Although it is possible that these three disorders arose independently, it is very likely that all three have the same etiologic cause, and we propose that a possible mechanism for this concurrence is related to maternal gestational diabetes. Maternal hyperglycemia mostly affects fetal structures deriving from the neural crest, including the palatine bone, and may have caused the cleft palate observed in this case. Gestational diabetes is also associated with increased frequency of large for gestational age infants and, by extension, with increased risk of birth injuries such as obstetric brachial plexus injury or congenital muscular torticollis associated with large for gestational age infants. Since the children of mothers with gestational diabetes are at increased risk for congenital defects such as cleft palate as well as being large for gestational age, precautions indicated for each respective disorder must be taken during prenatal testing and during birth. However, further studies of more cases are required to evaluate whether the concurrence of obstetric brachial plexus injury, congenital muscular torticollis and cleft palate in this case are complications specifically associated with gestational diabetes or just a simple coincidence.

• The Journal of the Korea Contents Association
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• v.17 no.7
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• pp.696-706
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• 2017

This study is to examine health care utilization and morbidity of disabled and non-disabled children in Korea to evaluate the health disparities. We used medical claim data of 2010 from the National Health Insurance Service-National Sample Cohort data. As a result of the analysis, the disabled children are not in good health condition because they have more frequency of medical service use, hospitalization rate, and more number of diseases and spent more on medical expenses than non-disabled children. Patterns of the most frequent disease differ from significantly between disable and non-disabled. Disabled children had a higher prevalence of selected birth defects and selected health conditions associated with physical disability and a lower prevalence of selected infection disease than children without disability. In conclusion, Health policy changes that would extend the access to health service for children with disabilities characterized by frequent medical care, hospitalization, excessive medical expenditure and complex diseases.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.242-246
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• 2009

The clinical features of ring chromosome 13 include mental and growth retardation, CNS anomalies, facial dysmorphism, cardiac defects, genital malformations, limb anomalies, skeletal deformities and anal malformations. Although many cases of ring chromosome 13 have been reported worldwide, only 6 cases have been reported in Korea, and the latter cases were not mosaic but pure ring chromosome 13. Here we report a case with mosaic ring chromosome 13. The baby boy was born at 37 weeks of gestation by induced vaginal delivery due to intrauterine growth restriction (IUGR). He was the second baby of a 28-year-old hepatitis B carrier mother and a 32-year-old father. There was no family history of chromosomal anomalies. The baby was a symmetric IUGR with a birth weight of 1,860 g, length of 44.8 cm, and head circumference of 29.4 cm. The physical examination revealed microcephaly, trigonocephaly, flat occiput, large ears, short neck and dysmorphic facial features, including microophthalmia, hypertelorism, antimongoloid slanting palpebral fissures, a flat nasal bridge, and micrognathia. The karyotype of this patient performed by peripheral blood lymphocytes was 46,XY,r(13)(p13q34)/45,XY,-13/46,XY,dic r(13;13)(p13q34;p13q34). The baby showed failure to thrive, hypotonia, and developmental delay. We report the first case of mosaic ring chromosome 13 in a male baby in Korea and compare this case with other Korean cases of non-mosaic ring chromosome 13.

• Journal of Oral Medicine and Pain
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• v.40 no.3
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• pp.110-114
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• 2015

Purpose: Growth and differentiation factor (GDF)-11 is a transforming growth factor-${\beta}$ family member that plays important regulatory roles in development of multiple tissues which include axial skeletal patterning, palatal closure, and tooth formation. Proteins that have been identified as GDF-11 inhibitors include GDF-associated serum protein (GASP)-1 and GASP-2. Recently, we found that mice genetically engineered to lack both Gasp1 and Gdf11 have an increased frequency of cleft palate. The goal of this study was to investigate the roles of GDF-11 and its inhibitors, GASP-1 and GASP-2, during dental and craniofacial development and growth. Methods: Mouse genetic studies were used in this study. Homozygous knockout mice for Gasp1 ($Gasp1^{-/-}$) and Gasp2 ($Gasp2^{-/-}$) were viable and fertile, but Gdf11 homozygous knockout ($Gdf11^{-/-}$) mice died within 24 hours after birth. The effect of either Gasp1 or Gasp2 deletion in $Gdf11^{-/-}$ mice during embryogenesis was evaluated in $Gasp1^{-/-}$;$Gdf11^{-/-}$ and $Gasp2^{-/-}$;$Gdf11^{-/-}$ mouse embryos at 18.5 days post-coitum (E18.5). For the analysis of adult tissues, we used $Gasp1^{-/-}$;$Gdf11^{+/-}$ and $Gasp2^{-/-}$;$Gdf11^{+/-}$ mice to evaluate the potential haploinsufficiency of Gdf11 in $Gasp1^{-/-}$ and $Gasp2^{-/-}$ mice. Results: Although Gasp2 expression decreased after E10.5, Gasp1 expression was readily detected in various ectodermal tissues at E17.5, including hair follicles, epithelium in nasal cavity, retina, and developing tooth buds. Interestingly, $Gasp1^{-/-}$;$Gdf11^{-/-}$ mice had abnormal formation of lower incisors: tooth buds for lower incisors were under-developed or missing. Although $Gdf11^{+/-}$ mice were viable and had mild transformations of the axial skeleton, no specific defects in the craniofacial development have been observed in $Gdf11^{+/-}$ mice. However, loss of Gasp1 in $Gdf11^{+/-}$ mice occasionally resulted in small and abnormally shaped auricles. Conclusions: These findings suggest that both GASP-1 and GDF-11 play important roles in dental and craniofacial development both during embryogenesis and in adult tissues.

• Journal of Korean Academy of Nursing
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• v.15 no.3
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• pp.62-73
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• 1985

The problems of growth & development due to maladjustment are gradually increasing while need for the treatment of children's diseases is decreasing. The level of developmental deficiency or delay correlates with neonatal birth weight and also with gestational age, i.e. degrees of prematurity. There-fore, developmental defects and potential risk factors' are more Common in premature infants than in full term infants. The purpose of this study is to define the difference in the growth at developmental status between premature and full term infants, and to define the relation between the developmental status and the physical growth during the first 3 years' Data were collected from January 10, 1985 to April 6, 1985 at 3 hospitals including St. Mary's Hospital, and through home visiting. The subjects of this study consisted of 79 Premature infants (G.A. <37wks. & B.W. <2.5kg) and 94 full term infants (G.A.≥37 wks. & B.W.≥2.5kg). The study method used was a questionnaire, anthropometric assessment and DDST for normative data of growth & development. The collected data were analyzed using descriptive statistics, chi-square test and t-test. The results of the study were as follows: Hypothesis: 1 : That the prematures will differ from the full term infants in the physical growth status during the first 3 years was partially supported (p＜0.02) : The prematures reached up the full term infants in the physical growth status in the first 6 months. And, the first hypothesis was supported (P<0.01) : There are more cases which is below‘the Korean children's physical. growth standards’in prematures than in full term infants. Hypothesis 2 : That the prematures will differ from the full term infants in the developmental status during the first 3 years was supported (P< 0.001)；‘Normal’developmental status due to DDST was less in prematures than in full term infants. And, the second hypothesis was Partially supported (P<0.02) : The developmental status of the pre-matures was different from that of the full term infants within the first 3 months by analysis of passed items in DDST, Hypothesis 3 : That the prematures' developmental status will relate to their physical growth during the first 3 years was supported (P<0.001) : If the prematures' developmental status is in delayed status, then, their physical growth status is also in delayed status. This study shows that the prematures differed significantly from the full term infants in the growth at developmental status during their infancy. This means that the nurse can foster the growth & development of the prematures by supportive care during their infancy. Further longitudinal study is needed to verify these findings for the environmental factors.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.47-51
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• 2016

Propionic acidemia (PA) is an autosomal recessively inherited disorder of the organic acid metabolism. It is caused by a deficiency of propionyl-CoA carboxylase (PCC). PCC is a heteropolymeric enzyme composed of ${\alpha}$- and ${\beta}$-subunits. The clinical symptoms of PA are heterogeneous and present vomiting, dehydration, hypotonia, and lethargy, and it can result in death. The typical presentations of neonatal onset PA are life-threatening metabolic acidosis and hyperammonemia. Here, we described a case of neonatal onset PA with mild clinical presentations. She was born to a healthy mother without complications. No significant illness was observed until nine days after birth. She started exhibiting poor oral feeding, vomiting, lethargy, and hypotonia at ten days old. Her laboratory results showed mild hyperammonemia and acidosis. The initial diagnosis was neonatal sepsis and she was treated with antibiotics. However, her clinical symptoms didn't improve. So we considered a metabolic disease. She was given nothing by mouth and intravenous hydration and nutrition support was performed. Propionylglycine and 3-hydroxypropionic acid were showed high concentrations in urine by gas chromatograph mass spectrometry (GC-MS). C3 level of acylcarnitine analysis elevated 10.4 uM/L (range, 0.200-5.00) in plasma. We took gene analysis for PA to be based on the symptoms and laboratory results. We detected PCCB gene mutation and diagnosed PA. She survived without severe neurologic defects and complications and was hospitalized only three times with upper respiratory tract infections for 7 years. We report a case of a ten days old neonate with PA presenting without severe metabolic acidosis and hyperammonemia who was effectively treated with early aggressive care and conventional methods.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.109-109
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• 2002

In recent reports, the multiple reproductive defects such as cryptorchidism, hypospadias, epididymal cysts, low sperm counts, and testicular cancers are increased in humans, and these changes were doubted by the chemicals with estrogenic or antiandrogenic activities in our environment. To compare the effects of neonatal exposure of di (n-butyl) phthalate and flutamide on the development of reproductive organs and to identify the specific mechanisms of these abnormalities related to the male reproducton, Sprague-Dawley neonate male rats were injected subcutaneously during 5-14 days after birth with corn oil (control), flutamide (0.05, 0.1, and 0.5 mg/animal) and DBP (5, 10, and 20 mg/animal). Animals were killed at 31 (immature) and 42 (pubertal) days of age respectively and blood was collected from abdominal aorta for serum testosterone analysis. Testes, epididymides, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscle (LABC), cowpers glands and glans penis were weighed. Expression of steroid hormone receptors (AR and ER) was examined in the testes and ventral prostate. At 31 days of age, ventral prostate, seminal vesicles, LABC, and cowpers glands significantly decreased in the flutamide (0.5 mg/animal) and DBP (20 mg/animal), but serum testosterone levels were not changed. Flutamide slightly delayed the testes descent at the high dose (0.5 mg/animal), but DBP did not show any significant effect on the testes descent at all doses. DBP and flutamide decreased the expression of AR protein in the testes but did not affect the expression of ERa and ER protein in the testes. At 42 days of age, ventral prostate, seminal vesicles, and cowpers glands weights were still significantly decreased at the high dose of flutamide (0.5 mg/animal) and DBP (20 mg/animal), but the weights of testes and epididymides were not different. Serum testosterone decreased significantly in DBP treated animals and slightly, not significantly, in flutamide group. While DBP still significantly decreased the expression of AR protein in testis, flutamide recovered from downregulation of AR protein and did not affect the expression of ERa and ER protein in the testes. Based on these results, flutamide and DBP have shown several similar patterns in reproductive abnormalitis, but some marked differences which may be caused by different acting mechanism.

• Child Health Nursing Research
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• v.6 no.1
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• pp.32-50
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• 2000

A descriptive exploratory design was used in this study to evaluate the effects of sponge bathing on physiological(heart rate, heart period, vagal tone, oxygen saturation, respiration) and behavioral responses in newly born 40 preterm infants from intensive care unit of S University Hospital in Seoul. Data has been collected from October, 1997 to March, 1999. The infants were between 27-33 weeks gestational age at birth, and were free of congenital defects. The subjects entered the protocol when they were medically stable (determined by initiation of feeding and discontinuation of all respiratory support) but still receiving neonatal intensive care. The infants' physiologic parameters were recorded a 10 - minute before, during, and after bathing. Continuous heart rate data were recorded on a notebook computer from the infant's EKG monitor. The data were digitized off-line on software(developed by Lee and Chang in Wavelet program) which detected the peak of the R wave for each heart beat and quantified sequential R-R intervals in msec(i.e. heart periods). Heart period data were edited to remove movement artifact. Heart period data were quantified as : 1) mean heart period; 2) vagal tone. Vagal tone was quantitfied with a noninvasive measure developed by Porges(1985) in Mxedit software. To determine behavioral status, tools were developed by Scafidi et al(1990) were used. Collected data were analyzed with the SPSS program using paried t-test, ANOVA, and Pearson correlation. The result were as follow. 1. The results of the ANOVAs indicated that vagal tone were signifcantly lower during bathing than baseline and post-bathing. There were significant differences in heart period and heart rate levels across the bathing. But the mean oxygen saturations and respirations were no differences. Also, there were no significant differences on behavioral sign, motor activity, behavioral distress, weight changes, morbidity, and hospitalization period. 2. To evaluate the relation between vagal tone and subsequent parameters, the two groups (the high group had 19 subjects and low group had 21subjects) were divided by the mean baseline vagal tone. Vagal tone measured prior to bathing were significantly associated with respiration before bathing, vagal tone during bathing, and the magnitude of change in both vagal tone. But, other subsequent reactivities were no differences in two groups. 3. Correlations were also calculated between vagal tone and the subsequent physiological reactivities from baseline through after- bathing. Correlations were significant between baseline vagal tone and baseline heart rate, between baseline vagal tone and baseline heart period, between baseline vagal tone and oxygen saturation after bathing. In summary, the bathing in this study showed a stressful stimulus on premature infants through there was significance in the physiological parameters. In addition, our study represents the documentation that vagal tone reactivity in response to clearly defined external stimulation provides an index of infant's status.