Molecular detection of Enterocytozoon bieneusi from bats in South Korea.

Enterocytozoon bieneusi, which has recently been re-classified as a fungus, was identified in 5.2% (3/58) bat intestinal tissues and 1.9% (4/210) bat feces collected in South Korea. The positive cases were classified into six genotypes including four novel genotypes, KBAT1-KBAT4, based on sequence analysis of the E. bieneusi internal transcribed spacer (ITS) region. In addition, a novel genotype, KBAT3, belonged to group 1, which is considered having zoonotic potential by phylogenetic analysis of the E. bieneusi ITS region. This study expands our knowledge of the host range of E. bieneusi.

Athletes' Expectations About Sport-Injury Rehabilitation: A Cross-Cultural Study.

CONTEXT: Athletes enter injury rehabilitation with certain expectations about the recovery process, outcomes, and the professional providing treatment. Their expectations influence the effectiveness of the assistance received and affect the overall rehabilitation process. Expectations may vary depending on numerous factors such as sport experience, gender, sport type, and cultural background. Unfortunately, limited information is available on athletes' expectations about sport-injury rehabilitation. OBJECTIVE: To examine possible differences in athletes' expectations about sport-injury rehabilitation based on their country of residence and type of sport (contact vs noncontact). DESIGN: Cross-sectional. SETTING: Recreational, college, and professional athletes from the US, UK, and Finland were surveyed. PARTICIPANTS: Of the 1209 athletes ranging from 12 to 80 y of age (mean 23.46 ± 7.91), 529 US [80%], 253 UK [86%], and 199 Finnish [82%] athletes provided details of their geographical location and were included in the final analyses. MAIN OUTCOME MEASURES: The Expectations About Athletic Training (EAAT) questionnaire was used to determine athletes' expectations about personal commitment, facilitative conditions, and the expertise of the sports-medicine professional (SMP). RESULTS: A 3 × 2 MANCOVA revealed significant main effects for country (P = .0001, ηp2 = .055) and sport type (P = .0001, ηp2 = .023). Specifically, US athletes were found to have higher expectations of personal commitment and facilitative conditions than their UK and Finnish counterparts. Athletes participating in contact sports had higher expectations of facilitative conditions and the expertise of the SMP than did athletes participating in noncontact sports. CONCLUSIONS: SMPs, especially those in the US, should consider the sport and environment when providing services. In addition, SMPs need to highlight and demonstrate their expertise during the rehabilitation process, especially for those who compete in contact sports.

Athletes' use of mental skills during sport injury rehabilitation.

CONTEXT: Existing theoretical frameworks and empirical research support the applicability and usefulness of integrating mental skills throughout sport injury rehabilitation. OBJECTIVE: To determine what, if any, mental skills athletes use during injury rehabilitation, and by who these skills were taught. Cross-cultural differences were also examined. DESIGN: Cross-sectional design. SETTING: College athletes from 5 universities in the United States and a mixture of collegiate, professional, and recreational club athletes from the United Kingdom and Finland were recruited for this study. PARTICIPANTS: A total of 1283 athletes from the United States, United Kingdom, and Finland, who participated in diverse sports at varying competitive levels took part in this study. MAIN OUTCOME MEASURES: As part of a larger study on athletes' expectations of injury rehabilitation, participants were asked a series of open-ended and closed-ended questions concerning their use of mental skills during injury rehabilitation. RESULTS: Over half (64.0%) of the sample reported previous experience with athletic training, while 27.0% indicated that they used mental skills during injury rehabilitation. The top 3 mental skills reported were goal setting, positive self-talk/positive thoughts, and imagery. Of those athletes that used mental skills, 71.6% indicated that they felt mental skills helped them to rehabilitate faster. A greater proportion of athletes from the United States (33.4%) reported that they used mental skills during rehabilitation compared with athletes from the United Kingdom (23.4%) and Finland (20.3%). A small portion (27.6%) of the participants indicated that their sports medicine professional had taught them how to use mental skills; only 3% were taught mental skills by a sport psychologist. CONCLUSIONS: The low number of athletes who reported using mental skills during rehabilitation is discouraging, but not surprising given research findings that mental skills are underutilized by injured athletes in the 3 countries examined. More effort should be focused on educating and training athletes, coaches, and sports medicine professionals on the effectiveness of mental training in the injury rehabilitation context.

Age-Related Changes in Low Serum Anti-Müllerian Hormone Levels in Female Adolescents: A Single-Center Retrospective Pilot Study.

STUDY OBJECTIVE: Available data on the clinical significance of low serum anti-Müllerian hormone (AMH) levels in female adolescents are limited. The aim of this study was to elucidate age-related changes in low serum AMH levels in adolescents and to identify predictive factors for AMH progression. METHODS: A retrospective review was conducted on a series of female adolescents aged 11-19 years with low serum AMH levels (<1.19 ng/mL) who underwent additional AMH tests at least 1 year apart. Participants who showed an increase in the subsequent AMH test (>1.6 ng/mL) (Group 1) were compared with those who did not (Group 2). RESULTS: Among 1655 adolescents who underwent AMH testing at least once from 2010 to 2022, 75 participants (4.5%) exhibited low AMH levels (<1.19 ng/mL), excluding primary ovarian insufficiency. A notable increase in serum AMH levels (>1.6 ng/mL) was confirmed in 7 (30.4%) of 23 female adolescents who underwent relevant follow-up testing. Group 1 had higher initial AMH levels and lower initial follicle-stimulating hormone levels than Group 2 (1.0 vs 0.59 ng/mL, P = .001 and 4.4 vs 9.8 mIU/mL, P = .015, respectively). Ovarian volume did not differ between the groups (3.8 vs 4.4 cm3, P = .465). None of the participants with initial AMH levels under 0.75 ng/mL showed an increase in AMH levels during follow-up. CONCLUSION: These findings suggest that low serum AMH levels in adolescents may have other explanations in addition to being indicative of a low ovarian reserve. Prospective studies involving a larger number of participants will aid in predicting AMH improvement in adolescents.

Cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders harboring RMRP mutations in two Korean children: A case report.

RATIONALE: Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene. PATIENT CONCERNS: Here, we report 2 cases of Korean children with CHH-AD. DIAGNOSES: In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES. INTERVENTIONS: The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups. OUTCOMES: Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis. LESSONS SUBSECTIONS: Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD.

How Can Restaurant Companies Effectively Deliver CSR Efforts to Consumers on Social Media?

This study emphasized the source credibility effect on consumers' responses to restaurant companies' CSR efforts on social media. Based on the source credibility brand development process (i.e., brand trust, brand affect, and brand engagement), this study employed an online survey-based experiment and revealed the meaningful associations among types of CSR posters (a restaurant brand vs. a nonprofit organization), brand trust, brand affect, and brand engagement. The empirical results indicated that the nonprofit organization has higher significant effects on brand trust and brand affect than those of the restaurant brand. Additionally, in the case of the nonprofit organization, the effects of brand trust and brand affect on brand engagement were significantly stronger than that of the restaurant brand. Based on the empirical findings, this study provided several theoretical and managerial implications for restaurant companies' CSR communication on social media.

Unpacking the Drivers of Dissatisfaction and Satisfaction in a Fitness Mobile Application.

This research investigates the factors influencing user satisfaction and dissatisfaction in fitness mobile applications. It employs Herzberg's two-factor model through text mining to classify Fitbit mobile app attributes into satisfiers and dissatisfiers. The Fitbit app was chosen due to its prevalence in the United States. The study analyzes 100,000 English reviews from the Fitbit app on the Google Play Store, categorizing attributes. It identifies three dissatisfying categories (functional, compatibility, paid services) and three satisfying categories (gratification, self-monitoring, self-regulation), comprising 25 sub-attributes. This classification offers in-depth insights into what drives user contentment or discontent with fitness apps. The findings contribute to the fitness app domain by applying text-mining and Herzberg's model. Researchers can build upon this foundation, and practitioners can use it to enhance app experiences. However, this research relies on user reviews, often lacking comprehensive explanations. This limitation may hinder a profound understanding of the underlying psychological aspects in user sentiments. Nonetheless, this study takes strides toward optimizing fitness apps for users and developers.

Health and weight attitudes of university recreation center leaders.

Objective: Emerging research suggests weight-neutral approaches to health promotion are effective in supporting overall health, but they have been minimally adopted within physical activity (PA) contexts. This is concerning as research shows PA-related professionals can perpetuate weight stigma, which can disrupt PA participation and enjoyment. Thus, the purpose of this study was to examine university recreation center (URC) leaders' attitudes toward health and weight. Participants and methods: One-hundred forty-one URC leaders completed the online Health and Weight Attitudes Scale. Results: Women and those who wanted to maintain weight had more positive attitudes toward not dieting than men (F (1,136)=5.090, p = 0.026, ηp2 = 0.036) and those who wanted to lose weight (p = 0.015). Participants' open-ended responses showed they held several misconceptions about the health and weight relationship and about weight-neutral eating and PA messaging. Conclusion: Educating PA professionals on weight-neutral approaches could benefit effective and inclusive PA and health promotion in URCs.

Maternal vitamin D deficiency in early pregnancy and perinatal and long-term outcomes.

Background: Vitamin D deficiency is common in pregnant women. Some studies have linked vitamin D deficiency to obstetric complications such as gestational hypertension, gestational diabetes, and preterm birth. Therefore, the objective of this study is to investigate the potential impact of vitamin D deficiency during pregnancy on both perinatal and long-term outcomes. Methods: In this retrospective study, conducted between 2017 and 2021, we analyzed the data of 1079 singleton pregnant women with no medical or surgical complications prior to pregnancy. We evaluated obstetric and perinatal outcomes, as well as neurodevelopmental outcomes using Bayley-III tests, Gross Motor Function Measure, or chart review. Results: The maternal serum vitamin D level in the first trimester was 18.2 ± 9.0 ng/mL. Vitamin D deficiency (<20 ng/mL) was found in 308 (62.0%) women in the first trimester, of which 288 women (26.7%) were in the very deficient group (<10 ng/mL). There were no differences in maternal age, body mass index, and previous preterm birth between the group with vitamin D < 10 ng/mL and ≥10 ng/mL group. There were also no differences in the rates of gestational hypertension, gestational diabetes, and preterm birth between the two groups, except for the rate of preterm birth before 37 weeks of gestation, which was significantly higher in the very deficient group (adjusted odds ratios [aOR] = 7.78, 95%CI [2.23-27.12], p = 0.001). In the very deficient group, the risk of developmental delay was also higher (aOR = 4.28, 95%CI [1.40-13.05], p = 0.011). Conclusions: This is the first study to analyze the effects of maternal vitamin D deficiency during pregnancy on both long-term developmental outcomes and perinatal prognosis. Vitamin D deficiency, defined as a level lower than 10 ng/mL in the first trimester, may increase the risk of preterm birth and developmental delay in children.

Adverse Effect of the Duration of Antibiotic Use Prior to Immune Checkpoint Inhibitors on the Overall Survival of Patients with Recurrent Gynecologic Malignancies.

PURPOSE: Antibiotic use preceding immune checkpoint inhibitor (ICI) treatment has been associated with a decreased efficacy of ICI in solid tumors. In this study, we evaluated the effect of antibiotic use before ICI therapy on oncological outcomes. METHODS: We examined patients with recurrent gynecologic malignancies at two academic institutions. The clinical data, including antibiotic use within 60 days of ICI initiation, type of antibiotics, reasons for antibiotic use, body mass index, tumor site, chemotherapy-free interval, prior history of radiotherapy, disease control rate (DCR), and overall survival (OS), were assessed. RESULTS: Of 215 patients, 22.9% (n = 47) received antibiotics before ICI treatment. The most common cancer was ovarian (52.1%, n = 112), followed by cervical (24.7%, n = 53) and endometrial (16.7%, n = 36). When we divided the cohort based on antibiotic use before ICIs, there were no significant differences in the DCR and baseline characteristics between the two groups. On multivariate analyses, the variables associated with poor OS were previous use of antibiotics for a cumulative duration of >14 days (HR 2.286, 95% CI 1.210-4.318; p = 0.011); Eastern Cooperative Oncology Group 2 or 3 (HR 4.677, 95% CI 2.497-8.762; p < 0.001); and chemotherapy-free interval of <6 months (HR 2.007, 95% CI 1.055-3.819; p = 0.034). CONCLUSION: Prior use of antibiotics for a cumulative duration of >14 days was associated with reduced survival in recurrent gynecologic malignancies.

First female Korean child with Coffin-Lowry syndrome: a novel variant in RPS6KA3 diagnosed by exome sequencing and a literature review.

Coffin-Lowry syndrome (CLS, OMIM # 303600) is a rare X-linked disorder caused by mutations in RPS6KA3. CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. Females with CLS are variably affected, complicating diagnosis. Here, we describe the clinical and molecular findings in a female Korean child with CLS and review the associated literature. A 5-year-old girl presented with short stature and developmental delays. She had a coarse facial appearance characterized by a prominent forehead, hypertelorism, thick lips, and hypodontia. She also had puffy tapering fingers and pectus excavatum. We performed exome sequencing and identified a novel, likely pathogenic, heterozygous variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in RPS6KA3 (NM_004586.2). This is the first Korean female genetically diagnosed with CLS. In contrast to the delayed bone age reported in previous studies, our patient showed advanced bone age and central precocious puberty. CLS should be considered as a differential diagnosis of short stature, tapering fingers, and developmental delay. We suggest that molecular techniques can be a useful tool for diagnosis of rare disorders such as CLS because such conditions are not simple, and the associated spectrum of phenotypes can vary.

Investigating the Effect of Compassion Fade in Volunteer Tourism.

This study investigated the relationship between the type of volunteer tourism (human vs. flora vs. fauna) and the type of message (individual with no statistic vs. individual with small statistic vs. individual with large statistic) and potential tourists' attitudes towards volunteer tourism and their intention to donate their time. To do so, this study conducted a between-subject 3 × 3 factorial design online experiment, where the influences of compassion fade on attitudes and behavioral intention to donate time for volunteer tourism, along with the impacts of positive affect, emotional involvement, and credibility, were examined. The results of the current study revealed that type of volunteer tourism and type of message do not affect attitude towards volunteer tourism and attitude towards the ad. Further analysis indicated that, among all three mediating variables, only positive affect mediated the relationship between type of volunteer tourism and attitude towards volunteer tourism, and all other hypotheses were not statistically significant. Moreover, the results indicated that there is a positive relationship between perceived ad credibility and attitude towards the ad, and also between perceived ad credibility and attitude towards volunteer tourism. The implications of these results are discussed based on the empirical findings.

Body fat distribution and insulin resistance among Korean middle-aged women: a Korean National Health and Nutrition Examination Survey.

OBJECTIVE: To evaluate menopause-related changes in body fat distribution and their relationship with insulin resistance in middleaged Korean women. METHODS: We analyzed women aged 40-60 years using data from the National Health and Nutrition Examination Survey conducted from 2008 to 2011. Body fat was measured using dual-energy X-ray absorptiometry. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Among 3,468 participants, menopausal women (n=1,489) had a higher body mass index (BMI) and higher trunk, arm, and head fat percentages than premenopausal women (n=1,979). However, no significant difference was found in the leg fat percentage according to menopausal status. Multivariable regression analysis for HOMA-IR showed that trunk fat percentage, BMI, and waist circumference positively correlated with insulin resistance and leg fat percentage negatively correlated after adjusting for several confounding factors, whereas menopausal status was not associated with HOMAIR. CONCLUSION: Middle-aged women not only have different body weights and BMI but also have different body fat distributions according to menopausal status. Each fat percentage change in the trunk and leg is differently associated with metabolic health, particularly insulin resistance. To evaluate the metabolic health of middle-aged women, BMI is generally noted; however, body fat distribution, which can be easily assessed using dual-energy X-ray absorptiometry, should also be considered.

Does CEO tenure moderate the link between corporate social responsibility and business performance in small- and medium-sized enterprises?

This study investigates the effect of CSR activities on business performance of small- and medium-sized enterprises (SMEs) in South Korea setting. Based on upper echelons theory and stakeholder theory, the study further examines CEO tenure as a potential moderator between CSR activities and business performance. The study considers four dimensions of CSR (economic, legal, ethical, and philanthropic) and two types of business performance (financial and non-financial). To test the moderating effect of CEO tenure, we divided the sample into two groups: companies with short-term tenured CEOs and long-term tenured CEOs. The data were collected from 443 CEOs of SMEs in South Korea. We used a multi-group analysis with SmartPLS 4. The study finds that CEO tenure moderates the relationship between dimensions of CSR and business performance. More specifically, the study finds that CEOs in early-stage tenure focus on philanthropic activities to drive financial performance, while their counterparts focus on economic/legal dimension. CEOs, regardless of the length of tenure, consider the philanthropic dimension helpful for improving both financial and non-financial performance. This study expands prior research by examining the relationship between CSR and business performance in SMEs, considering the impact of the CEO tenure. The findings of this study make contributions to the literature by demonstrating that CEO tenure is an important factor in linking CSR to business performance. This research also adds evidence to the CSR literature that economic and legal dimensions are considered mandatory responsibilities, and CEOs of SMEs view them as interconnected. For practical implications, this study identifies different predictors of financial performance for companies with short-term vs. long-term CEO tenure. Short-term CEOs focus on philanthropy to improve financial performance, and both long- and short-term CEOs believe that philanthropy affects the company's financial and non-financial performance.

Hypertriglyceridemia with acute pancreatitis in a 14-year-old girl with diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is a medically fatal condition in poorly controlled hyperglycemia or newly diagnosed diabetes mellitus. Severe hypertriglyceridemia (HTG) is an uncommon complication of DKA and can be associated with acute pancreatitis (AP). We present the clinical manifestations, laboratory findings, and management of AP associated with HTG in a 14-year-old girl with DKA. The patient, with a 7-year history of type 2 diabetes presented with epigastric pain, 1 month after stopping insulin injection. DKA, severe HTG, and AP were diagnosed based on the laboratory and imaging tests. She recovered from DKA after conventional treatment for DKA, and her triglyceride (TG) level was reduced from 10,867 mg/dL to the normal range after 7 days of admission without antilipid medication. Given that her C-peptide level was not too low and considering her negative diabetes-related antibodies and high TG level, targeted gene panel sequencing was performed on the genes associated with diabetes and HTG. We identified a heterozygous mutation, c.4607C>T (p. Ala1537Val), in ABCC8 related to maturityonset diabetes of the young (MODY) 12. To our knowledge, this is the first reported case of HTG-induced AP with DKA in a patient with MODY. In addition, we reviewed the literature for pediatric cases of HTG with DKA. In patients with DKA, timely awareness of severe HTG related to insulin deficiency is crucial for improving the consequences of AP. We recommend considering AP in all DKA patients presenting with severe HTG to ensure early and proper management.

Development and performance evaluation of an artificial intelligence algorithm using cell-free DNA fragment distance for non-invasive prenatal testing (aiD-NIPT).

With advances in next-generation sequencing technology, non-invasive prenatal testing (NIPT) has been widely implemented to detect fetal aneuploidies, including trisomy 21, 18, and 13 (T21, T18, and T13). Most NIPT methods use cell-free DNA (cfDNA) fragment count (FC) in maternal blood. In this study, we developed a novel NIPT method using cfDNA fragment distance (FD) and convolutional neural network-based artificial intelligence algorithm (aiD-NIPT). Four types of aiD-NIPT algorithm (mean, median, interquartile range, and its ensemble) were developed using 2,215 samples. In an analysis of 17,678 clinical samples, all algorithms showed >99.40% accuracy for T21/T18/T13, and the ensemble algorithm showed the best performance (sensitivity: 99.07%, positive predictive value (PPV): 88.43%); the FC-based conventional Z-score and normalized chromosomal value showed 98.15% sensitivity, with 40.77% and 36.81% PPV, respectively. In conclusion, FD-based aiD-NIPT was successfully developed, and it showed better performance than FC-based NIPT methods.

Wilson disease diagnosed incidentally by targeted gene panel sequencing in a Korean boy with severe obesity.

Wilson disease (WD) is a relatively common genetic hepatic disease in children and is characterized by excessive copper accumulation, predominantly in the liver and brain. It is an autosomal recessive disease caused by an ATP7B mutation that causes brain degeneration and is potentially fatal if diagnosed late or untreated. In the early phase of WD, its initial presentation may include mild hepatic involvement. WD may be overlooked as a cause of liver disease due to severe obesity but should not be excluded from differential diagnosis. We report a case of WD with severe obesity and fatty liver diagnosed in the early phase by targeted gene panel sequencing and review the endocrine problems associated with WD. Early suspicion of WD is important for good prognosis.

Development and Evaluation of AccuPower COVID-19 Multiplex Real-Time RT-PCR Kit and AccuPower SARS-CoV-2 Multiplex Real-Time RT-PCR Kit for SARS-CoV-2 Detection in Sputum, NPS/OPS, Saliva and Pooled Samples.

Rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the successful control of the current global COVID-19 pandemic. The real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) is the most widely used detection technique. This research describes the development of two novel multiplex real-time RT-PCR kits, AccuPower® COVID-19 Multiplex Real-Time RT-PCR Kit (NCVM) specifically designed for use with the ExiStation™48 system (comprised of ExiPrep™48 Dx and Exicycler™96 by BIONEER, Korea) for sample RNA extraction and PCR detection, and AccuPower® SARS-CoV-2 Multiplex Real-Time RT-PCR Kit (SCVM) designed to be compatible with manufacturers' on-market PCR instruments. The limit of detection (LoD) of NCVM was 120 copies/mL and the LoD of the SCVM was 2 copies/µL for both the Pan-sarbecovirus gene and the SARS-CoV-2 gene. The AccuPower® kits demonstrated high precision with no cross reactivity to other respiratory-related microorganisms. The clinical performance of AccuPower® kits was evaluated using the following clinical samples: sputum and nasopharyngeal/oropharyngeal swab (NPS/OPS) samples. Overall agreement of the AccuPower® kits with a Food and Drug Administration (FDA) approved emergency use authorized commercial kit (STANDARD™ M nCoV Real-Time Detection kit, SD BIOSENSOR, Korea) was above 95% (Cohen's kappa coefficient ≥ 0.95), with a sensitivity of over 95%. The NPS/OPS specimen pooling experiment was conducted to verify the usability of AccuPower® kits on pooled samples and the results showed greater than 90% agreement with individual NPS/OPS samples. The clinical performance of AccuPower® kits with saliva samples was also compared with NPS/OPS samples and demonstrated over 95% agreement (Cohen's kappa coefficient > 0.95). This study shows the BIONEER NCVM and SCVM assays are comparable with the current standard confirmation assay and are suitable for effective clinical management and control of SARS-CoV-2.

A boy with Coffin-Siris syndrome with a novel frameshift mutation in ARID1B.

Coffin-Siris syndrome (OMIM #135900) is an autosomal dominant inherited disorder, characterized by dysmorphic features, congenital anomalies, and developmental delay. We report the clinical and molecular findings in a patient with Coffin-Siris syndrome. A 3-year-and-6-month-old boy presented with developmental delay, distinctive facial features, hypertrichosis, partial agenesis of the corpus callosum, fifth digit nail hypoplasia, congenital anomalies, and growth retardation. Targeted gene panel sequencing identified a novel heterozygous frameshift mutation c.2147_2148insAC in ARID1B which was predicted as a premature stop codon p. (Gln717Argfs*29). This is the second report of Coffin-Siris syndrome in Korea. Targeted gene panel sequencing can be used as an effective tool for the diagnosis of rare complex syndromes such as Coffin-Siris syndrome.

Genetic Evaluation of Congenital Hypothyroidism with Gland in situ Using Targeted Exome Sequencing.

OBJECTIVE: To analyze the genetic causes of congenital hypothyroidism through the targeted exome sequencing of pediatric patients with congenital hypothyroidism with thyroid gland in situ. METHOD: The study population included 20 patients diagnosed with congenital hypothyroidism with thyroid gland in situ at the Pediatric Endocrinology Clinic of Pusan National University Hospital. Targeted exome sequencing was performed on eight causative genes, including thyroid stimulating hormone receptor (TSHR), mutation in which can cause hypothyroidism with a small or normal sized thyroid gland, and thyroglobulin (TG), thyroid peroxidase (TPO), dual oxidase 2 (DUOX2), dual oxidase maturation factor 2 (DUOXA2), iodotyrosine deiodinase (IYD), solute carrier family 26 member 4 (SLC26A4), and solute carrier family 5 member 5 (SLC5A5), mutations in which are known to cause thyroid dyshormonogenesis. RESULTS: Permanent, subclinical, and transient hypothyroidism were diagnosed in 15 (75%), three (15%), and two (10%) patients, respectively. Genetic mutations were identified in 16 patients (80% positivity rate). Targeted exome sequencing of eight genes identified 24 variants in these patients: 11 DUOX2 variants in eight patients; six TSHR variants in five patients; five TG variants in three patients; and two DUOXA2 variants in two patients. Of these 24 variants, 10 (41.6%) were novel. No variants were identified in TPO, IYD, SLC5A5, or SLC26A4. Two patients displayed triallelic (digenic) mutations (in TG and TSHR in one patient and DUOX2 and TSHR in the other). No variants were identified in three patients with permanent hypothyroidism and one patient with transient hypothyroidism. Genetic variations that could explain the congenital hypothyroidism phenotypes were identified in 12/15 cases (80%). CONCLUSIONS: Targeted exome sequencing identified the genetic causes of congenital hypothyroidism with thyroid gland in situ in 80% of the patients studied, with DUOX2 and TSHR mutations being the most common. As many of the identified variants were novel, additional studies on the genetic causes of congenital hypothyroidism are warranted.