Ki Wha Chung

Cymbidium goeringii is one of the most widely cultivated and traded ornamental orchids in East Asia. Due to its high horticultural value and phenotypic variability, accurate cultivar identification is essential but challenging, as their flowers bloom only briefly in spring. We have developed a forensic tool for rapid and exact cultivar discrimination by applying 12 simple sequence repeat (SSR) profiles in C. goeringii. This study was performed to establish an expanded SSR dataset for cultivar identification and phylogenetics in C. goeringii. We examined a total of 6,051 samples from 269 cultivars, including 92 Korean cultivars with ≥ 10 samples each. Among these, representative combined genotypes (CG1) were determined, and their frequencies (CG1%) were used to assess genetic concordance among samples. Phylogenetic trees were constructed using both Euclidean and codominant genetic distances, and cultivar distributions were visualized using Principal Coordinate Analysis (PCoA) and t-SNE. Approximately 72.8% of the samples matched their dominant combined genotype (CG1), suggesting that nearly 30% of cultivated orchids may exhibit genotype discordance. Phylogenetics and PCoA showed a weak or no correlation between phenotypes, while they revealed relatively clear clustering between Korean and Japanese origins. These results highlight the value of integrating multiple analytical methods to enhance interpretability. The expanded SSR genotype dataset presented here offers a robust resource for cultivar identification, verifying genotype concordance, phylogenetic analysis, and ecological genetics research. This study will be an important milestone in the forensic application of plants with diverse cultivars exhibiting a wide range of horticultural and commercial values.

A Novel LDB3 Mutation Identified in Patients with Late-Onset Myofibrillar Myopathy

Background and Aims: De novo mutations provide a fundamental source of gene pool changes, driving genomic microevolution. Charcot–Marie–Tooth disease (CMT), which is a group of genetically and clinically heterogeneous peripheral neuropathic disorders, is characterized by progressive muscle weakness, hand and foot deformities, and occasional involvement of other organs. This study conducted the first cohort study of de novo mutations in CMT patients. Methods: De novo mutations were examined in 151 genetically diagnosed father–mother–child trio autosomal dominant CMT families except for CMT1A. Results: We identified 49 de novo point or small indel mutations in 61 patients. The frequency of de novo mutations was 40.4%, with gene‐specific rates in their distribution. Haplotype analysis revealed predominant paternal origin, consistent with previous reports for CMT1A. Frequent substitutions at highly methylated CpG sites suggested that CpG methylation strongly contributes to the induction of de novo mutations. In particular, this study observed an anticipation of earlier onset in the affected children compared to their parents (founders) with de novo mutations. Interpretation: This study reports de novo mutations that occur frequently in CMT families. Characterization of de novo pathogenic mutations is expected to provide valuable insights not only into the genetic diagnosis and treatment of rare genetic diseases, but also into the evolutionary genomic study of deleterious alleles.

Objective: Early growth response protein 2 (EGR2) is a crucial transcription factor involved in peripheral nerve myelination. Mutations in EGR2 have been reported to cause severe forms of demyelinating neuropathy, including Charcot-Marie-Tooth disease type 1D (CMT1D), although the clinical phenotype may vary depending on the specific mutation site. In this study, we aimed to characterize the clinical, electrophysiological, and neuroimaging phenotypes of Korean Charcot-Marie-Tooth disease (CMT) patients and to identify EGR2 mutations through genetic analysis.Methods: Whole exome sequencing was conducted on CMT patients to identify pathogenic genetic variants. Clinical evaluations included neurological examinations, motor and sensory nerve conduction studies, and magnetic resonance imaging (MRI) analysis of the lower limbs in patients harboring EGR2 mutations. In silico analyses were performed to assess the potential functional impacts of the identified mutations on the EGR2 protein structure.Results: Four EGR2 mutations were identified, including the novel p.D355E variant. Patients carrying the p.R359W, p.R381H, and p.R381L mutations exhibited early onset and rapid progression of symptoms, whereas the patient with the p.D355E mutation presented with symptom onset in the late 30s and demonstrated milder clinical manifestations into their 40s. MRI findings in the p.D355E patient suggested preservation of deep posterior compartment muscles, contrasting with observations in other mutation cases. In silico predictions indicated that the p.D355E mutation is likely to result in less pronounced structural changes in EGR2, potentially explaining the observed phenotypic differences.Conclusion: This study demonstrates that clinical variability among EGR2 mutations is correlated with the characteristics and positions of amino acid substitutions. Our findings contribute to the expanding database of EGR2 mutations, enhancing the understanding of diagnosis and prognosis in demyelinating neuropathies.

Background and Aims: The SLC5A6 gene encodes a transmembrane protein responsible for transporting biotin, pantothenic acid, and lipoic acid. Mutations in SLC5A6 have shown a wide spectrum of clinical phenotypes, such as sodium‐dependent multivitamin transporter deficiency (SMVTD), childhood‐onset biotin‐responsive peripheral motor neuropathy (COMNB), and mixed axonal and demyelinating sensory motor neuropathy. The purpose of this study was to identify pathogenic SLC5A6 mutations in the Korean CMT cohort.Methods: This study performed whole exome sequencing to identify the genetic cause for two independent patients with early onset axonal sensorimotor polyneuropathy and SMVTD. We also examined the therapeutic effects of multivitamin replenishment on a patient with SLC5A6 mutations.Results: We identified compound heterozygous variants of SLC5A6 in two patients (p.Arg94X and p.Phe522Ser in patient 1; p.Cys443Tyr and p.Phe513_Lys515delinsLeu in patient 2). In patient 2, an oral regimen comprising biotin, lipoic acid, and pantothenic acid demonstrated significant therapeutic effects, including cessation of cyclic vomiting, resolution of skin lesions on the fingers, and improvements in muscle weakness affecting both the upper and lower extremities.Interpretation: This study represents the first report of novel heterozygous SLC5A6 mutations in patients with axonal CMT and SMVTD, expanding the phenotypic spectrum associated with SLC5A6 mutations. Notably, we observed significant therapeutic effects from multivitamin treatment in a patient.

Background Somatic mosaicism is caused by a postzygotic de novo mutation. It is a very rare genetic event, and mosaic cases have been reported only very limitedly among Korean patients with peripheral neuropathies, including Charcot-Marie-Tooth disease (CMT) so far. Objective This study was performed to identify and characterize somatic mosaicism in Korean families with CMT. Methods Genetic causes were identified by whole exome sequencing (WES) and a subsequent filtering process of the variants. The level of mosaicism for the de novo somatic mutations was determined by counting altered sequences from approximately 100 colonies/mutation and the ratio of altered sequences per total reads at the mutation site using the WES data. Results We observed two cases of somatic mosaicism in different families with CMT: p.Cys104Tyr in INF2 (male with CMT1) and p.Ser729Arg in TRPV4 (female with CMT2). The approximate levels of mosaicism were determined to be 24% and 30% in the blood, respectively. A man with the INF2 mutation showed very mild symptoms, while a woman with the TRPV4 mutation showed severe clinical phenotypes. The INF2 mutation is specifically considered a case of gonadal mosaicism. In addition, we confirmed that the p.Cys104Tyr in INF2 is associated with the CMT1 phenotype without focal segmental glomerulosclerosis (FSGS). Conclusion This study may be the first or second report for the INF2 and TRPV4 mosaicism. The degrees of the phenotypic severity for the mosaic mutations probably depend on the mutation sites and the levels of mosaicism in the affected tissues. This study suggests that somatic mosaicism may contribute to inter- or intra-familial phenotypic heterogeneity.

Variable copy number variations (CNVs) in the short arm of chromosome 17 are associated with many neurodevelopmental disorders, including Charcot–Marie–Tooth disease type 1A, Potocki–Lupski syndrome and Yuan–Harel–Lupski syndrome. Here we examined CNVs in two sporadic cases of developmental abnormalities, brain impairment and peripheral neuropathy. We identified novel duplications of approximately 14.1 Mb at 17p11.2–p13.1 (containing PMP22 and RAI1 ) and 17.6 Mb at 17p11.2–p13.3 ( YWHAE , PAFAH1B and PMP22 ) in each patient. Both duplications were suggested to be produced by de novo mutations of paternal origin. This study suggests that CNVs at 17p should be examined in patients with peripheral neuropathy as well as developmental and brain abnormalities.

The biodiversity and distribution of epiphytic orchids are strongly influenced by their relationship with host plants, and environmental variables like elevation, slope, and local climate are key factors in determining the abundance and diversity of these orchids. The aim of this study was to examine the richness of orchid species at different elevations within the research area of Nepal. Sampling was conducted at elevations ranging from 1300 m to 2800 m above sea level, using a systematic sampling technique known as belt transects. Six circular plots with a diameter of 5.6 m were established in a horizontal transect at each site, spaced at least 50 m apart, with 100 elevation interval. The analysis revealed a hump-shaped relationship between orchid species richness and elevation, with the highest species richness observed at altitude of 2100–2200 m. The abundance of orchids was significantly correlated with host characteristics, including habit (shrub/tree), bark texture, nature (deciduous/evergreen), and physical factors. This study underscores the significant contribution of host characteristics and environmental factors in explaining the diversity of epiphytic orchid species along the elevation of the Himalayas.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity. As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was done in four patients, and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.