Chun-Jui Huang

A systematic review of genetic studies of thyroid disorders in Taiwan

Abstract A systematic review of genetic studies of thyroid disorders in Taiwan identified studies of gene mutations involved in the synthesis and binding of thyroid hormone, as well as mutations of proto‐oncogenes and tumor suppressor genes in thyroid cancer. Studies related to gene polymorphisms in patients with autoimmune thyroid disease (AITD) and thyroid cancer were also reviewed. The most prevalent mutations in the Han‐Chinese population were c.2268insT in the thyroid peroxidase (TPO) gene and c.919‐2A>G in the Pendred syndrome (PDS) gene. Additional mutations have also been revealed in the genes encoding TPO (n = 5), thyroglobulin (TG; n = 6), pendrin (n = 2), and thyroxine‐binding globulin (TBG; n = 2), which were novel at the time they were reported. The prevalence of various somatic mutations in differentiated thyroid cancer was similar in Taiwan and Western countries, with the RAS kinase mutation and tyrosine receptor kinase (TRK) and rearranged during transfection (RET) proto‐oncogenes being detected in lower frequencies and the B‐type RAF kinase (BRAF) mutation accounting for the majority of cases. Recent microRNA analysis revealed an association between miR146b and the BRAF mutation, which was associated with poor prognosis of papillary thyroid carcinoma (PTC). Susceptibility to Graves’ disease (GD) was linked to the human leukocyte antigen (HLA) region. The associated alleles were different in Han‐Chinese and Caucasians; HLA‐DPB1*0501, the major allele in Taiwan, has a low frequency in the West. By contrast, a high frequency of HLA‐DRB1*0301 was detected in Caucasians but not Han‐Chinese. In addition to the HLA region, cytotoxic T lymphocyte‐associated molecule‐4 (CTLA4) gene polymorphisms +49G>A and +6230G>A (CT60) were positively associated with GD. The GG genotype and G allele of single nucleotide polymorphism (SNP) +49G>A were also related to relapse of Graves’ hyperthyroidism after antithyroid drug withdrawal. Differences in the genetic patterns between Han‐Chinese and Caucasians for some thyroid disorders suggest the importance of variable genetic influences in different populations.

A Novel mutation in the SLC26A4 gene in a Chinese family with Pendred syndrome

OBJECTIVE To investigate the mutations in the SLC26A4 gene in a Chinese patient with Pendred syndrome. METHODS The diagnosis of Pendred syndrome was confirmed by the family history, pure tone audiogram, perchlorate discharge test (PDT), and computed tomography (CT) of the temporal bone. DNA extraction, PCR and DNA sequencing were performed according to standard procedures. Mutations in the SLC26A4 gene were compared with 100 unrelated subjects to exclude common polymorphism. Splice-site mutation was further confirmed by restriction enzyme length polymorphism (RFLP) with the specifically designed primers. RESULTS The proband presented with typical features of bilateral sensorineural deafness since childhood and goiter development in the early adulthood. Thyroid studies disclosed euthyroidism with elevated thyroglobulin, but negative for PDT. Marked enlargement of bilateral vestibular aqueduct (>1.5 mm) was found by CT of the temporal bone. A novel SLC26A4 splice-site mutation c.1263+1G>A (IVS10+1G>A) was identified in compound heterozygosity with the missense mutation c.1079C>T (p.A360V) in the proband. Both mutations were not found in the 100 unrelated Chinese. CONCLUSIONS Our results support previous findings that Pendred syndrome can be caused by compound heterozygous mutation in the SLC26A4 gene, in which IVS10+1G>A is a novel pathogenic mutation.

Iodine Nutritional Status of School Children in Nauru 2015

Little is known about iodine nutritional status in island countries in the Pacific Ocean. The primary objective of this study was to report for the first time the iodine nutritional status of people in Nauru. In addition, sources of iodine nutrition (i.e., water and salt) were investigated. A school-based cross-sectional survey of children aged 6–12 years was conducted in three primary schools of Nauru. Urinary iodine concentration (UIC) was determined by spot urine samples. Available water and salt samples in Nauru were collected for the measurement of iodine content. A food frequency questionnaire was conducted. The median UIC was 142 μg/L, and 25.2% and 7.4% of the population had median UIC below 100 μg/L and 50 μg/L, respectively. Natural iodine-containing foods such as seaweeds and agar were rare. Iodine was undetectable in Nauruan tank water, filtered tap water, and raindrops. Of the analyzed salt products, five kinds were non-iodized, and three were iodized (iodine content: 15 ppm, 65 ppm, and 68 ppm, respectively). The results indicate that the iodine status in Nauruan school children is adequate. Iodized salt may serve as an important source of iodine nutrition in Nauru.

A novel mutation of KCNJ11 gene in a patient with permanent neonatal diabetes mellitus

A 4-month-old male baby was diagnosed with Permanent Neonatal Diabetes Mellitus. We identified a novel missense heterogeneous mutation in the KCNJ11 gene at codon 167 (aTC→tTC) in a region that corresponds to a predicted intracellular gate of the ATP-sensitive potassium channel.

Iodine Status of Taiwanese Population in 2013: 10 Years After Changing From Mandatory to Voluntary Salt Iodization:

Background: In 2003, Taiwan’s iodine policy changed from mandatory to voluntary. The Nutrition and Health Survey in Taiwan (NAHSIT) 2001-2002 for schoolchildren showed adequate iodine nutrition, while NAHSIT 2005-2008 for adults showed the iodine status was at borderline adequacy. Objective: To investigate the iodine status of the Taiwanese population from schoolchildren to adulthood 10 years after the change of the salt iodization policy. Method: Urinary iodine was measured in samples from subjects in NAHSIT 2013. Results: The median urinary iodine concentration (UIC) of the Taiwanese population aged 6 years and above in 2013 was 96 μg/L, indicating mild iodine deficiency. The median UIC of 6- to 12-year-old schoolchildren was 124 μg/L (interquartile range [IQR]: 92-213 μg/L), and 115 μg/L (IQR: 80-166 μg/L), 125 μg/L (IQR: 74-161 μg/L), 73 μg/L (IQR: 52-131 μg/L), and 78 μg/L (IQR: 52-132 μg/L) in populations aged 13 to 18 years, 19 to 44 years, 45 to 64 years, and ≥65 years, respectively. Declining iodine nutrition in age groups ≥45 years old was noted that the median UIC of populations aged 45 to 64 years and ≥65 years was 99 and 88 μg/L, respectively, in NAHSIT 2005-2008. The median UIC of schoolchildren was not lower than that during the mandatory salt fortification period, but the distribution of urinary iodine levels signified a dietary pattern change. Conclusion: Wide-ranging variation in iodine nutrition levels was observed in different age groups. Universal salt iodization, as suggested by the World Health Organization, should be the best strategy to achieve adequate iodine nutrition.

Paravesical (urachal) paraganglioma (PGL) presenting as hypertensive crisis during micturition, mimicking bladder PGL

a Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan b Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan c Institute of Public Health, National Yang-Ming University, Taipei, Taiwan d Department of Urology, Taipei Veteran General Hospital, Taipei, Taiwan e School of Medicine, National Yang-Ming University, Taipei, Taiwan

A study of primary hypophysitis, i.e., two cases of lymphocytic hypophysitis and one IgG4-related variant: The importance of measuring serum IgG4 levels to allow early diagnosis and prompt treatment for the IgG4-related variant.

a Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan b Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan c Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan d Division of Endocrinology and Metabolism, Department of Medicine, Taoyuan Branch of Taipei Veterans General Hospital, Taoyuan, Taiwan