• Journal of Genetic Medicine
• /
• v.16 no.2
• /
• pp.71-75
• /
• 2019

Periventricular nodular heterotopia (PNH) is a malformation of cortical development in which normal neurons inappropriately cluster in periventricular areas. Patients with Mowat-Wilson syndrome (MWS) typically present with facial gestalt, complex neurologic problems (e.g., severe developmental delay with marked speech impairment and epilepsy), and multiple anomalies (e.g., Hirschsprung disease, urogenital anomalies, congenital heart defects, eye anomalies, and agenesis of the corpus callosum [CC]). MWS is mostly caused by haploinsufficiency of the gene encoding zinc-finger E-box-binding homeobox 2 (ZEB2) due to premature stops or large deletions. We present a case report of a 9-year-old girl with PNH, drug-responsive epilepsy, severe intellectual disability, and facial dysmorphisms only in whom we performed whole-exome sequencing and found a de novo heterozygous missense mutation (c.3134A>C; p.His1045Pro) of ZEB2 (NM_014795.3; NP_055610.1). This mild case of MWS caused by a rare novel missense mutation of ZEB2 represents the first report of MWS with isolated PNH.

• Clinical and Experimental Pediatrics
• /
• v.50 no.8
• /
• pp.789-793
• /
• 2007

Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, is a rare autosomal dominant disorder characterized by variable manifestations, including multiple basal cell carcinomas, odontogenic keratocysts of the jaw, skeletal anomalies including scoliosis and bifid ribs, palmar and plantar pits, calcification of the falx cerebri, and biparietal frontal bossing. We report a case of a 9-year-old boy with the clinical features of basal cell nevus syndrome, in which a PTCH gene mutation was confirmed by DNA testing.

• Clinical and Experimental Pediatrics
• /
• v.56 no.8
• /
• pp.355-358
• /
• 2013

Kabuki syndrome (KS) is a rare genetic disease with a distinctive dysmorphic face, intellectual disability, and multiple congenital abnormalities. KS is inherited in an autosomal dominant manner. As the primary cause of KS, MLL2 mutations have been identified in 56-76% of affected individuals who have been tested, suggesting that there may be additional genes associated with KS. Recently, a few KS individuals have been found to have de novo partial or complete deletions of an X chromosome gene, KDM6A, which encodes a histone demethylase that interacts with MLL2. Nevertheless, mutations in MLL2 are the major cause of KS. Although there are a few reports of KS patients in Korea, none of these had been confirmed by genetic analysis. Here, we report a case of a Korean patient with clinical features of KS. Using direct sequencing, we identified a frameshift heterozygous mutation for MLL2 : (c.5256_5257delGA;p.Lys1753Alafs$^*34$). Clinically, the patient presented with typical facial features, and diagnosis of KS was based on the diagnostic criteria. While KS is a rare disease, other malformations that overlap with those found in individuals with KS are common. Hence, the diagnosis of KS by mutational analysis can be a valuable method for patients with KS-like syndromes. Furthermore, in the near future, other genes could be identified in patients with KS without a detectable MLL2 mutation.

• Plant Breeding and Biotechnology
• /
• v.6 no.4
• /
• pp.354-362
• /
• 2018

Maize has high food and industrial value, whereas has difficulties in research because of their complex and huge size genome. Nested association mapping (NAM) was constructed to better understand maize genetics. However, most studies were conducted using the reference genome B73, and only a few studies were conducted on tropical maize. Ki3, one of the founder lines of the NAM population, is a tropical maize. We analyzed the genetic characteristics of Ki3 by using RNA sequencing and bioinformatics tools for various genetic studies. As results, a total of 30,526 genes were expressed, and expression profile were constructed. A total of 1,558 genes were differentially expressed in response to drought stress, and 513 contigs of them come from de novo assemblies. In addition, high-density polymorphisms including 464,930 single nucleotide polymorphisms (SNPs), 21,872 multiple nucleotide polymorphisms (MNPs) and 93,313 insertions and deletions (InDels) were found compared to reference genome. Among them, 15.0 % of polymorphisms (87,838) were passed non-synonymous test which could alter amino acid sequences. The variants have 66,550 SNPs, 5,853 MNPs, and 14,801 InDels, also proportion of homozygous type was higher than heterozygous. These variants were found in a total of 15,643 genes. Of these genes, 637 genes were found as differentially expressed genes (DEGs) under drought stress. Our results provide a genome-wide analysis of differentially expressed genes and information of variants on expressed genes of tropical maize under drought stress. Further characterization of these changes in genetic regulation and genetic traits will be of great value for improvement of maize genetics.

• BMB Reports
• /
• v.54 no.2
• /
• pp.98-105
• /
• 2021

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a family of DNA sequences originally discovered as a type of acquired immunity in prokaryotes such as bacteria and archaea. In many CRISPR systems, the functional ribonucleoproteins (RNPs) are composed of CRISPR protein and guide RNAs. They selectively bind and cleave specific target DNAs or RNAs, based on sequences complementary to the guide RNA. The specific targeted cleavage of the nucleic acids by CRISPR has been broadly utilized in genome editing methods. In the process of genome editing of eukaryotic cells, CRISPR-mediated DNA double-strand breaks (DSB) at specific genomic loci activate the endogenous DNA repair systems and induce mutations at the target sites with high efficiencies. Two of the major endogenous DNA repair machineries are non-homologous end joining (NHEJ) and homology-directed repair (HDR). In case of DSB, the two repair pathways operate in competition, resulting in several possible outcomes including deletions, insertions, and substitutions. Due to the inherent stochasticity of DSB-based genome editing methods, it was difficult to achieve defined single-base changes without unanticipated random mutation patterns. In order to overcome the heterogeneity in DSB-mediated genome editing, novel methods have been developed to incorporate precise single-base level changes without inducing DSB. The approaches utilized catalytically compromised CRISPR in conjunction with base-modifying enzymes and DNA polymerases, to accomplish highly efficient and precise genome editing of single and multiple bases. In this review, we introduce some of the advances in single-base level CRISPR genome editing methods and their applications.

• Journal of Life Science
• /
• v.31 no.8
• /
• pp.771-777
• /
• 2021

Human endogenous retroviruses (HERVs) were inserted into the human genome millions of years ago but they are currently inactive and non-infectious due to recombinations, deletions, and mutations after insertion into the host genome. Nonetheless, recent studies have shown that HERV-derived elements are actually involved in physiological phenomena and certain diseases including cancers. Among the various physiological phenomena related to HERV-derived elements, it is necessary to focus on inflammatory response. HERV-derived elements have been reported to be directly involved in various inflammatory diseases, including autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, amyotrophic lateral sclerosis, and Sjogren's syndrome. As a mechanism for regulating inflammation through HERV-derived elements, the possibility that HERV-derived elements may cause nonspecific innate immune processes and that HERV-derived RNA or proteins may cause selective signaling mechanisms through specific receptors can be considered. However, the mechanism through which HERV-derived elements regulate inflammatory response, such as how silent HERV elements are activated in inflammatory response and what factors and signaling mechanisms are involved in HERV-derived elements, have not been identified to date, making it difficult to study the onset of HERV-related inflammatory disease. In this review, we introduce HERV-related autoimmune diseases and propose the mechanisms of HERV-derived elements at the molecular level of HERV in inflammatory response.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.5
• /
• pp.984-991
• /
• 1998

Background: The 3p deletions has been shown to be the most frequent alteration in lung cancers, strongly suggesting the presence of at least one tumor suppressor gene in this chromosomal region. However, no solid candidate for the tumor suppressor gene(s) on 3p has as yet been identified. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT, which is located in a region that is homozygously deleted in multiple tumor cell lines and disrupted by the hereditary renal cell carcinoma t(3;8) chromosomal translocation breakpoint FHIT also spans FRA3B, the most common fragile sites in the human genome. In the present study, we have analyzed expression of the FHIT gene in lung cancer cell lines. Methods: RNA from 21 lung cancer cell lines (16 NSCLC, 5 SCLC) were extracted using standard procedures. Random-primed. first strand cDNAs were synthesized from total RNA and PCR amplication of coding exons 5 to 9 was performed. The RT-PCR products were electrophoresed in 1.5% ethidium bromide-stained agarose gels. Results: 12 of 21(57%) lung cancer cell lines exhibited absent or aberrant FHIT expression [7 of 16(44%) of non-small cell lung cancer and 5 of 5(100%) of small cell lung cancer cell lines]. Conclusion: The result shows that abnormal transcription of the FHIT gene is common in human lung cancer cell lines, especially in small cell lung cancer.