• Journal of Genetic Medicine
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• v.20 no.1
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• pp.25-29
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• 2023

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother. Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.2
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• pp.133-147
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• 2005

Objectives: This study was carried out to establish human embryonic stem cells derived from frozen-thawed embryos using mouse embryonic fibroblasts (mEFs), human fetal skin and muscle fibroblasts as feeder cells, and to identify the characteristic of embryonic stem cells. Methods: When primary mEFs, human fetal skin and muscle fibroblasts were prepared, passaging on 4 days from replating could have effective trypsinization and clear feeder layers. Eight of 23 frozenthawed 4~8 cell stage embryos donated from consenting couples developed to blastocysts. Inner cell mass (ICM) was isolated by immunosurgery. ICM was co-cultured on mEFs, human fetal skin or muscle fibroblasts. The ICM colonies grown on mEFs, human fetal skin or muscle fibroblasts were tested the expression of stage specific embryonic antigen-3, -4 (SSEA-3, -4), octamer binding transcription factor-4 mRNA (Oct-4) and alkaline phosphatase surface marker. Results: We obtained 1 ICM colony from 2 ICM co-cultured on mEFs as feeder cells and did not obtain any ICM colony from 6 ICM clumps co-cultured on human fetal skin or muscle fibroblasts. The colony formed on mEFs could be passaged 30 times every 5 days with sustaining undifferentiated colony appearance. When the colonies cultured on mEFs were grown on human fetal skin or muscle fibroblasts, the colonies could be passaged 15 times every 9 days with sustaining undifferentiated colony appearance. The colonies grown on mEFs and human fetal fibroblasts expressed SSEA-4 and alkaline phosphatase surface markers and positive for the expression of Oct-4 by reverse transcription-polymerase chain reaction (RT-PCR). The produced embryoid body differentiated spontaneously to neural progenitorlike cells, neuron-like cells and beating cardiomyocyte-like cells, and frozen-thawed embryonic stem cells displayed normal 46,XX karyotype. Conclusions: The human embryonic stem cells can be established by using mEFs and human fetal fibroblasts produced in laboratory as feeder cells.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.5 no.1
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• pp.108-117
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• 1994

Twenty nine children with autism and thirty children with mental retardation were examined for association between autism and chromosomal disorders including fragile X. The peripheral blood was cultured in Medium 199 with methotrexate and without methorexate for 70 hours. Thirty metaphase cells in each case were karyotyped in all samples. Chromosomal abnormalities were found in 11 cases(37.9%) of autistic disorder and 10 cases (33.3%) of mental retardation, but in none of fragile(X)(q27.3) from all cases. Chromosomal abnormalities were present on group A, C, D and X in autistic disorder and on group A, B, C, D, E and X in mental retardation. No specific chromosomal region was found in both autistic disorder and mental retardation. Types of chromosomal disorders were only fragile and/or gap but no numerical abnormality was present in all cases. Number of cells which revealed fragile sites were 31 cells(3.6%) out of 870 cells in autistic disorder and 29 cells(3.2%) out of 900 cells in mental retardation Number of cells which revealed gaps were 43 cells(4.9%) out of 870 cells in autistic disorder and 35 cells(3.9%) out of 900 cells in mental retardation. Autistic disorder may not be directly correlated with fragile X but with nonspecific chromosomal breakages from these data.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.95-99
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• 2009

Prenatal diagnosis of rare autosome mosaicism involvingchromosomes other than chromosome 13, 18, 21 or the sex chromosome is encountered prognostic dilemma during genetic counseling. We report four cases of level III uncommon mosaicism of trisomy 5, 16 and 20,diagnosed prenatally. In case 1 with mosaic trisomy 20, there was a higher mosaic ratio of trisomy 20 in the repeat amniocentesis (62.1%) than in the first (36.6%) with normal fetal ultrasound finding except for a relatively small aorta on a 3-vessel view of the fetal heart. Case 2 showed a low rate of mosaic trisomy 20 (5.25%) in cultured amniocytes but normal karyotype in the repeat amniocentesis, who delivered a normal healthy baby. Case 3 showed a 13.6% of trisomy 16 mosaicism in the 30 cells of cultured amniocytes. Sixty cells from a fetal blood sample at termination showed non-mosaic 46,XX normal karyotype, while skin fibroblasts had 22.5% trisomy 16 in 40 metaphases. The autopsy showed ventricular septal defect (VSD). Case 4 with low grade mosaicism (10.5%) of trisomy 5 resulted in elective termination, though the ultrasoumd showed growsly normal fetus. Although level III mosaicism is regarded as true mosaicism, it is difficult to predict the outcome of the fetus with rare mosaic autosome trisomy. Therefore mosaic autosome trisomy of fetus should be carefully interpreted with more various approaches including repeat sampling and targeted fetal ultrasound.