• Journal of Genetic Medicine
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• v.18 no.2
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• pp.127-131
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• 2021

Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by ataxia, intellectual disability, cerebellar atrophy, macrocephaly, coarse face, and absent speech. It is caused by loss-of-function mutations in SNX14. To date, all cases with homozygous pathogenic variants have been identified in consanguineous families. This report describes the first Korean cases of SCAR20 family caused by homozygous variants in SNX14. Two siblings were referred to our clinic because of severe global developmental delay. They presented similar facial features, including a high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose. Because the older sibling was unable to walk and newly developed ataxia, repeated brain magnetic resonance imaging (MRI) was performed at the age of 4 years, revealing progressive cerebellar atrophy compared with MRI performed at the age of 2 years. The younger sibling's MRI revealed a normal cerebellum at the age of 2 years. Whole-exome sequencing was performed, and homozygous variants, such as c.2746-2A>G, were identified in SNX14 from the older sibling. Sanger sequencing confirmed homozygous SNX14 variants in the two siblings as well as a heterozygous variant in both parents. This report extends our knowledge of the phenotypic and mutational spectrum of SCAR20. We also highlight the importance of deep phenotyping for the diagnosis of SCAR20 in individuals with developmental delay, ataxia, cerebellar atrophy, and distinct facial features.

• Genomics & Informatics
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• v.19 no.4
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• pp.39.1-39.8
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• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• Journal of Genetic Medicine
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• v.19 no.1
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• pp.22-26
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• 2022

Cerebrotendinous xanthomatosis (CTX) is a rare genetic disease caused by a deficiency of enzymes for the synthesis of bile acid, resulting in the accumulation of cholestanol with reduced chenodeoxycholic acid (CDCA) production and causing various symptoms such as chronic diarrhea in infancy, juvenile cataracts in childhood, tendon xanthomas in adolescence and young adulthood, and progressive neurologic dysfunction in adulthood. Because oral CDCA replacement therapy can effectively prevent disease progression, early diagnosis and treatment are critical in CTX. This study reports the case of CTX in a 10-year-old male who presented with Achilles tendon xanthoma and mild intellectual disability. Biochemical testing showed normal cholesterol and sitosterol levels but elevated cholestanol levels. Genetic testing showed compound heterozygous variants of CYP27A1, c.379C>T (p.Arg127Trp), and c.1214G>A (p.Arg405Gln), which confirmed the diagnosis of CTX. The patient had neither cataracts nor other focal neurologic deficits and showed no abnormalities on brain imaging. The patient received oral CDCA replacement therapy without any adverse effects; thereafter, the cholestanol level decreased and no disease progression was noted. The diagnostic possibility of CTX should be considered in patients with tendon xanthoma and normolipidemic conditions to prevent neurological deterioration.

• Journal of Genetic Medicine
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• v.19 no.1
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• pp.32-37
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• 2022

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal disorder caused by the deficiency of arylsulfatase B due to mutations in the ARSB gene. Here, we report the case of a Korean female with a novel variant of MPS VI. A Korean female aged 5 years and 8 months, who is the only child of a healthy non-consanguineous Korean couple, presented at our hospital for severe short stature. She had a medical history of umbilical hernia and recurrent otitis media. Her symptoms included snoring and mouth breathing. Subtle dysmorphic features, including mild coarse face, joint contracture, hepatomegaly, and limited range of joint motion, were identified. Radiography revealed deformities, suggesting skeletal dysplasia. Growth hormone (GH) provocation tests revealed complete GH deficiency. Targeted exome sequencing revealed compound heterozygous mutations in the ARSB genes c.512G>A (p.Gly171Asp; a pathogenic variant inherited from her father) and c.1157C>T (p.Ser386Phe; a novel variant inherited from her mother in familial genetic testing). Quantitative tests revealed increased urine glycosaminoglycan (GAG) levels and decreased enzyme activity of arylsulfatase B. While on enzyme replacement therapy and GH therapy, her height increased drastically; her coarse face, joint contracture, snoring, and obstructive sleep apnea improved; urine GAG decreased; and left ventricular mass index was remarkably decreased. We report a novel variant-c.1157C>T (p.Ser386Phe)-of the ARSB gene in a patient with MPS VI; these findings will expand our knowledge of its clinical spectrum and molecular mechanisms.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.27 no.3
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• pp.243-246
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• 1982

A proposal of gene transfer scheme from diploid to hexaploid in oats was described. The main idea of this scheme are (1) use Avena magna which has two genomes partially in common with two genomes of the hexaploid Avena sativa or a common genome and the rest genomes partially commonn, and which lead to more regular pairing between them rather than AABB genome type to get 6x-amphiploid as a bridge between ploidy level. Cross between Avena strigosa and Avena magna is compatible and further give 42% seed set, (2) extract tetraploid derivatives which have in corporated desired genes from Avena strigasa to Avena magna, (3) Synthetic petaploid provide 2n=21 chromosome number in female gametes, which lead to complete pairing or nearly so in progenies with Avena sativa, (4) eventually homozygous lines will be produced by selfing the heterozygous (regarding to$A^{As}$ genome) at final step.

• Journal of Yeungnam Medical Science
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• v.40 no.3
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• pp.283-288
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• 2023

Severe chronic neutropenia is classified as severe congenital, cyclic, autoimmune, or idiopathic. However, there is a lot of uncertainty regarding the diagnosis of severe congenital neutropenia (SCN) and chronic idiopathic neutropenia, and this uncertainty affects further evaluations and treatments. A 20-year-old man presented with fever and knee abrasions after a bicycle accident. On admission, his initial absolute neutrophil count (ANC) was 30/µL. He had no medical history of persistent severe neutropenia with periodic oscillation of ANC. Although his fever resolved after appropriate antibiotic therapy, ANC remained at 80/µL. Bone marrow (BM) aspiration and biopsy were performed, and a BM smear showed myeloid maturation arrest. Moreover, genetic mutation test results showed a heterozygous missense variant in exon 4 of the neutrophil elastase ELANE: c597+1G>C (pV190-F199del). The patient was diagnosed with SCN. After discharge, we routinely checked his ANC level and monitored any signs of infection with minimum use of granulocyte colony-stimulating factor (G-CSF), considering its potential risk of leukemic transformation. Considering that SCN can be fatal, timely diagnosis and appropriate management with G-CSF are essential. We report the case of a patient with SCN caused by ELANE mutation who had atypical clinical manifestations. For a more accurate diagnosis and treatment of severe chronic neutropenia, further studies are needed to elucidate the various clinical features of ELANE.

• The korean journal of orthodontics
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• v.53 no.5
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• pp.336-342
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• 2023

Objective: To determine whether the gonial angle on digital panoramic radiographs is associated with vitamin D receptor (VDR) Taql polymorphism. Methods: Genomic DNA samples were collected from the buccal mucosa of patients aged 26-43 years. TaqMan assay for single nucleotide polymorphism genotyping was used to detect the genotype of Taql polymorphism. The gonial angle was measured bilaterally on panoramic radiography. The normal gonial angle was fixed as 121.8°, and it represented the cutoff value for the high gonial angle (HGA) and low gonial angle (LGA) groups. Various genetic models were analyzed, namely dominant (homozygous [AA] vs. heterozygous [AG] + polymorphic [GG]), recessive (AA + AG vs. GG), and additive (AA + GG vs. AG), using the chi-squared test. Results: The reliability of the gonial angle measurement was analyzed using a random sample (26%) of the tests, with the intra-examiner correlation showing an intra-class correlation coefficient of 0.99. The frequencies of the AA, AG, and GG genotypes of rs731236 polymorphism were 40.5%, 41.9%, and 17.6% in the HGA group and 21.8%, 51.0%, and 27.2% in the LGA group, respectively (P = 0.042). A statistically significant difference was observed in the allele frequencies between the two groups (P = 0.011). Moreover, a significant correlation was observed in the dominant genetic model. Conclusions: Taql polymorphism in the VDR gene plays a critical role in the vertical growth of the mandible and decreased gonial angle.

• Genomics & Informatics
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• v.20 no.4
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• pp.42.1-42.11
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• 2022

Breast cancer (BC) is a significant threat to female health, with both modifiable and non-modifiable risk factors. It is essential to monitor patients regularly and to raise population awareness. Increasing research also suggests that E-selectin (SELE) may increase tumor angiogenesis and the development of cancer. This study investigated SELE single-nucleotide polymorphisms (SNPs) in the following positions: rs5367T/C, rs5368C/T, rs5362T/G, and rs5362T/C. Using polymerase chain reaction, significant differences in allele and genotype frequencies were found between BC patients and controls. Position rs5368 was associated with an increased risk of BC for the CT and TT genotypes, with odds ratios (ORs) of 16.3 and 6.90 (Fisher probability = 0.0001, p = 0.005). Women with the T allele had a 19.3-fold higher incidence of BC, while allele C may be a protective allele against BC (OR, 0.05). Heterozygous genotypes at rs5367, rs5362, and rs5362 were significantly more common in BC patients, with ORs of 5.70, 4.50, and 3.80, respectively. These SNPs may be associated with the risk of BC, because the frequency of mutant alleles was significantly higher in patients (OR: 4.26, 3.83, and 4.30, respectively) than in controls (OR: 0.23, 0.30, and 0.20, respectively). These SNPs may be considered a common genotype in the Iraqi population, with the wild-type allele having a protective fraction and the mutant allele having an environmental fraction. The results also revealed a 2-fold increase in gene expression in BC patients compared to controls, with a significant effect (p = 0.017). This study's findings confirm the importance of SELE polymorphisms in cancer risk prediction.

• Journal of the Korean Child Neurology Society
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• v.25 no.3
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• pp.204-207
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• 2017

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH syndrome) is a neurometabolic disorder with highly variable clinical severity ranging from mild learning disability to severe encephalopathy. Diagnosis of HHH syndrome can easily be delayed or misdiagnosed due to insidious symptoms and incomplete biochemical findings, in that case, genetic testing should be considered to confirm the diagnosis. HHH syndrome is caused by biallelic mutations of SLC25A15, which is involved in the urea cycle and the ornithine transport into mitochondria. Here we report a boy with spastic paraplegia and asymptomatic younger sister who have compound heterozygous mutations of c.535C>T (p.R179^*) and c.116C>A (p.T39K) in the SLC25A15 gene. We identified that p.T39K mutation is a novel pathogenic mutation causing HHH syndrome and that p.R179^*, which is prevalent in Japanese and Middle Eastern heritage, is also found in the Korean population.

• Fisheries and Aquatic Sciences
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• v.26 no.9
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• pp.569-581
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• 2023

The morphology and genetic identification of Rasbora lateristriata and Rasbora argyrotaenia between cultivated and wild populations has never been reported. This study compares morphology and cytochrome c oxidase (COI) genes between farmed and wild stock Rasbora spp. in Java and Sumatra island, Indonesia. We analyzed the truss network measurement (TNM) characters of 80 fish using discriminant function analysis statistical tests. DNA was extracted from muscle tissue of 24 fish specimens, which was then followed by polymerase chain reaction, sequencing, phylogenetic analysis, fixation index analysis, and statistical analysis of haplotype networks. Basic Local Alignment Search Tool analysis validated the following species: R. lateristriata and R. argyrotaenia from farming (Jogjakarta); Rasbora agryotaenia (Purworejo), R. lateristriata (Purworejo and Malang), Rasbora dusonensis (Palembang), and Rasbora einthovenii (Riau) from natural resources. Based on TNM characters, Rasbora spp. were divided into four groups, referring to four distinct characters in the middle of the body. The phylogenetic tree is divided into five clades. The genetic distance between R. argyrotaenia (Jogjakarta) and R. lateristriata (Malang) populations (0.66) was significantly different (p < 0.05). R. lateristriata (Purworejo) has the highest nucleotide diversity (0.43). R. argyrotaenia from Jogjakarta and Purworejo shared the same haplotype. The pattern of gene flow among them results from the two populations' close geographic proximity and environmental effects. R. argyrotaenia had low genetic diversity, therefore, increasing heterozygosity in cultivated populations is necessary to avoid inbreeding. Otherwise, R. lateristriata (Purworejo) had a greater gene variety that could be used to develop breeding. In conclusion, the middle body parts are a distinguishing morphometric character of Rasbora spp., and the COI gene is more heterozygous in the wild population than in farmed fish, therefore, enrichment of genetic variation is required for sustainable Rasbora fish farming.