Mothers against decapentaplegic homolog (SMAD) proteins are intracellular mediators of members of the transforming growth factor-β (TGF-β) superfamily, which are activated by bone morphogenetic proteins (BMPs). On activation, SMAD5 forms heterometric SMAD complexes, which are translated to the nucleus where they regulate gene transcription. TGF-β induces T cell activation and cardiovascular disease, two important features of Kawasaki disease (KD), whereas BMP is associated with coronary artery disease. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) of SMAD5 may be associated with KD and coronary arterial lesions (CALs). Genotyping for 15 SNPs of the SMAD5 gene (rs3764941, rs10085013, rs6596284, rs7356756, rs13179769, rs13166063, rs1109158, rs4585442, rs4146185, rs12719481, rs6865297, rs3206634, rs6871224, rs1057898, and rs7031) was performed by direct sequencing of 105 KD patients and 303 healthy adult controls. We also compared the allele frequencies between a CAL group (n = 31) and a normal coronary group (n = 74). Results showed that among the 15 SNPs, rs3206634 was significantly associated with KD in a recessive model (odds ratio = 2.31, p = 0.019), whereas there was no association between any of the 15 SNPs and CALs. These findings may be used as a risk factors development of KD or for future generations of therapeutic treatments for KD.

Background/Aims: Syndromes of reduced sensitivity to thyroid hormone can be caused by innate resistance to thyroid hormone (RTH), thyroid hormone cell transporter defects, or thyroid hormone metabolism defects. This study was performed to describe clinical, endocrinological, and molecular characteristics of patients with disorders associated with impaired sensitivity to thyroid hormone due to THRB or SLC16A2 mutations. Methods: This study included 5 probands (1 male and 4 females) with RTH and 6 patients with Allan-Herndon-Dudley syndrome (AHDS). Clinical features and endocrine findings were reviewed retrospectively. Molecular analysis of two candidate genes, THRB or SLC16A2, confirmed the diagnosis. Results: Among RTH patients, median age at diagnosis was 5.6 years. Three patients were classified as having generalized RTH, whereas the other 2 patients were regarded as having isolated pituitary RTH. Three novel heterozygous mutations and 2 known mutations in THRB were identified from 5 independent pedigrees. All mutations were located in the major ligand-binding domain. In AHDS patients, delayed development was apparent between 3 and 6 months of age. Direct sequencing of SLC16A2 identified 6 hemizygous missense mutations in each patient: p.I188N, p.G221R, p.A224V, p.G276R, p.W398R, and p.G401R. Conclusions: This study identified 3 novel mutations in THRB in RTH patients and 1 novel mutation in SLC16A2 in AHDS patients. Routine neonatal screening based on the TSH assay has a limited role in detecting RTH or AHDS. Therefore, genetic testing of the candidate genes THRB and SLC16A2 should be performed for diagnosis of RTH and AHDS in patients with the suggestive clinical phenotype.

Purpose Predicted adult height (PAH) is often crucial to decision-making about treatment with human growth hormone (GH) or gonadotropin-releasing hormone agonist in children with short stature. This study compares final adult height (FAH) with different methods used to determine PAH and assesses the clinical utility and analytical validity of height prediction for children not treated with GH.Methods Clinical findings were retrospectively analyzed, and the heights of 44 children (22 males and 22 females) who visited our clinic between August 2006 and June 2017 and reached near final adult height (NFAH) were evaluated. Children treated with GH were excluded. We compared measured NFAH to PAH using the Bayley-Pinneau (BP), Tanner-Whitehouse Mark 2, and Roche-Wainer-Thissen (RWT) methods.Results Pearson correlation between all 3 prediction methods and NFAH showed high positive correlations in males and females (P<0.05). The average difference between PAH and NFAH for the BP method (0.4±3.9 cm) was significantly lower than those for the RWT and TW 2 methods in females (P=0.000, analysis of variance). Furthermore, only PAH by the BP method in females was very close to measured NFAH (paired t-test). A Bland-Altman plot verified that 95% of the differences between the PAH and NFAH exist between limits of agreement (mean±1.96 standard deviation).Conclusions The BP method is more useful to predict NFAH in females than other methods. Careful attention is still required when using such tools because PAH can be inaccurate. Therefore, a more accurate FAH prediction model for Korean children is needed.

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Metabolic syndrome (MetS) is an emerging burden associated with significant morbidity and mortality in children and adolescents.In recent decades, the prevalence of obesity has continually increased both worldwide and in Korea. 1,2 Trends in mean body mass index (BMI) have recently flattened for both boys and girls in northwestern Europe and Asia-Pacific regions, for boys in southwestern Europe, and for girls in central and Latin America. 1 In contrast, the rise in BMI has accelerated for both boys and girls in east and South Asia, and for boys in Southeast Asia. 1 Pediatric obesity is often accompanied by MetS. Consequently, accurate evaluation of obesity in children and adolescents is of significant interest because it may result in adulthood obesity and comorbid conditions such as cardiovascular disease, obstructive sleep apnea, insulin resistance, non-alcoholic fatty liver disease, and dyslipidemia. 3,4 More than half of all obese children have two or more complications. The definition of MetS by the modified criteria of the National Cholesterol Education Program-Adult Treatment Panel III must include at least three of five criteria: central obesity above the 90th percentile, fasting glucose above 110 mg/dL, hypertriglycerides above 110 mg/dL, low high density lipoprotein cholesterol below 40 mg/dL, and hypertension above the 90th percentile or receiving treatment for hypertension. 1 Based on the criteria of the International Diabetes Federation, MetS is a combination of central obesity with the presence of two or more of the other four risk factors. 5According to International Diabetes Federation guidelines, children younger than 6 years are excluded from the definition due to limited data for this age group. MetS cannot be diagnosed at the age of 6 to 10 years. However, additional testing should be performed if there is a family history of MetS, type 2 diabetes mellitus, dyslipidemia, cardiovascular disease, hypertension, or obesity. 6 Most studies are based on baseline BMI measurements to evaluate excessive adiposity in humans. BMI is a limited indicator of pediatric metabolic risk due to the paucity of data in this population. 7 Waist circumference (WC) and waist-height ratio (WHtR) are helpful measures of central adiposity in both clinical and research settings. 8 WC has emerged as an index of pediatric adiposity that predicts fat mass as effectively as or better than BMI. 8 Moreover, WC has been shown to be effective in estimating total adiposity, which is strongly linked to intra-abdominal fat.Several studies have investigated the prevalence of abdominal obesity in children and adolescents and report that it ranges from 9.7% to 11.5% in Korea. [9][10][11] Compared with previous studies, 9-11 the