The First Korean Family With Hereditary Gelsolin Amyloidosis Caused by p.D214Y Mutation in the GSN Gene

Hereditary gelsolin amyloidosis (HGA) is an autosomal dominant hereditary disease characterized by corneal lattice dystrophy, peripheral neuropathy, and cutis laxa. So far, no Korean patients with HGA have been reported. A 58-yr-old man presented with involuntary facial twitching, progressive bilateral facial weakness, and tongue atrophy. His mother, maternal uncle, two sisters, and son suffered from the same symptoms. Electrophysiological studies revealed signs of chronic denervation in the cervical and lumbar regions, mild sympathetic autonomic dysfunction, and bilateral facial nerve dysfunction. Diagnostic whole-exome sequencing (WES) revealed a p.D214Y heterozygous mutation in the gelsolin gene in affected members. We present the first report of a Korean family with HGA diagnosed by WES. WES facilitated a clinical diagnosis of HGA in patients with undiagnosed neuropathies.

Adeno-Associated Virus 2-Mediated Hepatocellular Carcinoma is Very Rare in Korean Patients

BACKGROUND: The incidence and etiology of hepatocellular carcinoma (HCC) vary widely according to race and geographic regions. The insertional mutagenesis of adeno-associated virus 2 (AAV2) has recently been considered a new viral etiology of HCC. The aim of this study was to investigate the frequency and clinical characteristics of AAV2 in Korean patients with HCC. METHODS: A total of 289 unrelated Korean patients with HCC, including 159 Hepatitis-B-related cases, 16 Hepatitis-C-related cases, and 114 viral serology-negative cases, who underwent surgery at the Samsung Medical Center in Korea from 2009 to 2014 were enrolled in this study. The presence of AAV2 in fresh-frozen tumor tissues was investigated by DNA PCR and Sanger sequencing. The clinical and pathological characteristics of AAV2-associated HCC in these patients were compared with previous findings in French patients. RESULTS: The AAV2 detection rate in Korean patients (2/289) was very low compared with that in French patients (11/193). Similar to the French patients, the Korean patients with AAV2-related HCC showed no signs of liver cirrhosis. The Korean patients were younger than the French patients with the same AAV2-associated HCC; the ages at diagnosis of the two Korean patients were 47 and 39 yr, while the median age of the 11 French patients was 55 yr (range 43-90 yr). CONCLUSIONS: AAV2-associated HCC was very rare in Korean patients with HCC. Despite a limited number of cases, this study is the first to report the clinical characteristics of Korean patients with AAV2-associated HCC. These findings suggest epidemiologic differences in viral hepatocarcinogenesis between Korean and European patients.

A Population-Based Genomic Study of Inherited Metabolic Diseases Detected Through Newborn Screening

BACKGROUND: A newborn screening (NBS) program has been utilized to detect asymptomatic newborns with inherited metabolic diseases (IMDs). There have been some bottlenecks such as false-positives and imprecision in the current NBS tests. To overcome these issues, we developed a multigene panel for IMD testing and investigated the utility of our integrated screening model in a routine NBS environment. We also evaluated the genetic epidemiologic characteristics of IMDs in a Korean population. METHODS: In total, 269 dried blood spots with positive results from current NBS tests were collected from 120,700 consecutive newborns. We screened 97 genes related to NBS in Korea and detected IMDs, using an integrated screening model based on biochemical tests and next-generation sequencing (NGS) called NewbornSeq. Haplotype analysis was conducted to detect founder effects. RESULTS: The overall positive rate of IMDs was 20%. We identified 10 additional newborns with preventable IMDs that would not have been detected prior to the implementation of our NGS-based platform NewbornSeq. The incidence of IMDs was approximately 1 in 2,235 births. Haplotype analysis demonstrated founder effects in p.Y138X in DUOXA2, p.R885Q in DUOX2, p.Y439C in PCCB, p.R285Pfs*2 in SLC25A13, and p.R224Q in GALT. CONCLUSIONS: Through a population-based study in the NBS environment, we highlight the screening and epidemiological implications of NGS. The integrated screening model will effectively contribute to public health by enabling faster and more accurate IMD detection through NBS. This study suggested founder mutations as an explanation for recurrent IMD-causing mutations in the Korean population.

DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population

BACKGROUND: Most cases with congenital hypothyroidism (CH) are usually sporadic, while about 20% of the cases are caused by genetic defects. Little information is available regarding the mutation incidence and genetic heterogeneity of CH in Koreans. We aimed to determine the mutation incidence of CH in newborn screenings (NBS) and to evaluate the frequency and spectrum of mutations underlying CH. METHODS: A total of 112 newborns with thyroid dysfunction were enrolled from 256,624 consecutive NBS. Furthermore, 58 outpatients with primary CH were added from an endocrine clinic. All coding exons of TSHR, PAX8, TPO, DUOX2, DUOXA2, and SCL5A5 were sequenced. RESULTS: The mutation incidence of CH was estimated to be 1 in 6,580 newborns. A total of 36 different mutations were identified in 53 cases. The overall mutation positive rate was 31%. The DUOX2 mutations were the most prevalent in both newborns and outpatients. Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH. CONCLUSIONS: The mutation incidence of CH was considerably higher than expected in the Korean newborn population. This study revealed seven different recurrent mutations underlying CH. We conclude that DUOX2 mutations are a frequent cause of CH in the Korean population.

Vitamin B12 Content Using Modified Microbioassay in Some Korean Popular Seaweeds, Fish, Shellfish and Its Products

There is a limitation to estimate vitamin B12 intake due to a lack of data on vitamin B12 content in many Korean foods. In this study, vitamin B12 content was determined in some seaweeds, fish, and shellfish and their product that are consumed in Korea using a modified microbioassay with Lactobacillus delbruecki ATCC 7830. Dried laver and dried seasoned and toasted laver contained very high levels of vitamin B12 (66.8 and 55.2-71.3 microg/100 g, respectively. Sea lettuce and seaweed fulvescene also contained high vitamin B12 content of 5.47-9.41 and 6.46-7.20 microg/100 g, respectively, whereas sea mustard and sea tangle contained low levels of vitamin B12; vitamin B12 was not detected in seaweed fusifome. Pacific saury, trout, sea-bass, or squid contained 12.01, 2.00, 0.49 and 2.33 microg vitamin B12/100 g, respectively. Ochellatus octopus, and naked sand lance contained 0.72-1.43 and 3.68 microg vitamin B12/100 g, respectively. Dried Alaska pollack contained 0.19-2.64 microg vitamin B12/100 g. Shellfish such as little neck clam and small ark shellfish contained high levels of vitamin B12 of 30.5-40.5 microg/100 g, and mussel and abalone contained 17.71 and 7.82 microg/100 g, respectively. Of unique Korean traditional fermented seafood products, salt-fermented products of squid (2.91 microg/100 g), clams (34.31 microg/100 g), Alaska pollack roe (9.98-12.02 microg/100 g), hairtail guts (4.58 microg/100 g) or small shrimp (0.58-1.55 microg/100 g), and fish sauce from anchovies (1.52-1.78 microg/100 mL), sand eel (0.22-0.24 microg/100 mL) or small shrimp (0.19-0.78 microg/100 mL) were analyzed. A few commercial brands of flying fish roe (0.73-1.73 microg/100 g), canned tuna (0.40 microg/100 g), and fried fish paste (0.25-0.69 microg /100 g) were also analyzed. In conclusion, vitamin B12 content in these foods, chosen considering the Korean food culture, should contribute to improve the present vitamin B12 food database. It may be helpful to estimate vitamin B12 intake more correctly than before, and provide additional information for dietary education related to vitamin B12 and meal management.

Vitamin B12 content analysis of favorite Korean restaurant foods, convenient foods and bakery products

There is a limitation to estimate vitamin B12 intake due to the lack of data on vitamin B12 content of Korean commercial foods. In this study, vitamin B12 content was determined in favorite Korean restaurant foods, convenient or instant foods, fast foods and bakery products through a modified microbioassay using Lactobacillus delbrueckii ATCC 7830. Bulgogi and seafood & green pepper griddle had high vitamin B12 content, 3.50 and 2.96 microg/100 g, respectively. Pork suyook, pork griddle and pollack griddle had 0.48, 0.31 and 0.32 microg/100 g of vitamin B12, respectively. In stew, soft-tofu stew with seafood and doenjang stew with seafood had relatively high vitamin B12 content, 1.93 and 1.44 microg/100 g, respectively. Bibimbap and 4 different types of rice porridge, beef & mushroom, chicken & ginseng, seafood or abalone, had 0.36, 0.08, 0.09, 1.64 and 0.13 microg/100 g of vitamin B12, respectively. One serving of haejanggguk, yookejang, chuotang and galbitang had 5.97, 2.04, 2.63 and 1.91 microg of vitamin B12, respectively. One serving of samgetang and sulongtang had 2.89 microg and 6.64 microg of vitamin B12. In noodles, one serving of cram noodle soup, bibim-nangmyeon, and mul-nangmyeon had 18.8, 1.21 and 0.38 microg of vitamin B12, respectively. One regular gimbap and one triangle gimbap contained 1.09-2.53 and 0.54-1.11 microg of vitamin B12, respectively. One cheese-burger, chicken-burger and bulgogi-burger had 0.76, 0.62 and 0.54 microg of vitamin B12, respectively. A plain bagel and a waffle contained 0.13 and 0.17 microg/100 g of vitamin B12, respectively. Ready-made tomato sauce or cream sauce for spaghetti in a retort pouch contained only a trace of vitamin B12. In conclusion, these results should contribute to improving the present food vitamin B12 content database, most of which were cited from foreign data, thereby it could be helpful to estimate the vitamin B12 intake of Koreans more accurately than before. It will also provide new information for dietary education related to vitamin B12 and health.