Comparative Genomic Analysis of Staphylococcal Cassette Chromosome mec Type V Staphylococcus aureus Strains and Estimation of the Emergence of SCCmec V Clinical Isolates in Korea
2024; 44(1): 47-55
Ann Lab Med 2020; 40(4): 326-330
Published online July 1, 2020 https://doi.org/10.3343/alm.2020.40.4.326
Copyright © Korean Society for Laboratory Medicine.
Jong Eun Park , M.D.1, Sun Ae Yun , M.T.2, Eun Youn Roh , M.D.3, Jong Hyun Yoon , M.D.3, Sue Shin , M.D.3, and Chang-Seok Ki, M.D.4
1Department of Laboratory Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea; 2Center for Clinical Medicine, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; 3Department of Laboratory Medicine, Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea; 4GC Genome, Yongin, Korea
Correspondence to: Sue Shin, M.D.
Department of Laboratory Medicine, Boramae Hospital, Seoul National University College of Medicine, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea
Tel: +82 2-870-2602 Fax: +82 2-870-2620. E-mail: jeannie@snu.ac.kr
Chang-Seok Ki, M.D.
GC Genome, 107 Ihyeon-ro 30beon-gil, Giheung-gu, Yongin 16924, Korea
Tel: +82-31-260-0601 Fax: +82-31-260-9087. E-mail: changski.md@gmail.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by progressive proximal muscle weakness and atrophy. Given the recent introduction of gene therapies, knowledge of the SMA carrier frequency in various populations has become important for developing screening programs for this disease. In total, 1,581 anonymous DNA samples from an umbilical cord blood bank were tested for
Keywords: Korea, Spinal muscular atrophy, Carrier frequency, multiplex ligation-dependent probe amplification
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by progressive proximal muscle weakness and atrophy resulting from degeneration of the alpha motor neurons of the anterior horn of the spinal cord. SMA is phenotypically heterogeneous and is classified into four clinical subtypes based on the age of onset and motor function achieved [1]. Type I SMA presents marked weakness and developmental motor regression before the age of six months and usually results in death within two years. Type II SMA presents before the age of 18 months and is associated with difficulty in walking independently. Type III SMA presents after the age of 18 months and individuals walk independently with only supportive care and is seldom fatal. Type IV SMA presents in the second or third decade of life, with only minor muscle weakness. The incidence of all types of SMA is estimated to be 1 in 10,000 live births globally [2].
SMA is caused by variants in
In December 2016, the US Food and Drug Administration approved nusinersen (SPINRAZA™, Biogen, Cambridge, MA, USA), the first effective treatment for SMA (www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm534611.htm). Nusinersen is a modified antisense oligonucleotide that binds to a specific sequence, including exon 7 of
In total, 1,581 anonymous DNA samples obtained from a public umbilical cord blood bank (Seoul Metropolitan Government Cord Blood Bank, Seoul, Korea) were used. This study protocol was exempted from review by the Institutional Review Board (IRB) of Seoul National University Boramae Hospital, Seoul, Korea (07-2019-17) because the samples have been kept as a repository study under the approval of IRB. All samples were collected from mothers who provided informed consent for donation and research use of their cord blood. The MLPA analysis has been conducted since July 2019.
The MLPA assay was conducted using SALSA MLPA probemix P460-A1 SMA kits (MRC-Holland, Amsterdam, Netherlands), according to the manufacturer's instructions (https://www.mlpa.com/WebForms/WebFormDBData.aspx?FileOID=_ImdLw-TiaZY.). The PCR products were analyzed using an ABI PRISM 3100 ABI Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). The data were analyzed using GeneMarker software, version 2.6 (Softgenetics, State College, PA, USA). Gene frequencies were calculated with VassarStats (http://vassarstats.net/), with 95% CI. The Hardy-Weinberg equilibrium was assessed by a professional web-based program (https://wpcalc.com/en/equilibrium-hardy-weinberg/).
The distribution of
In this study, the
According to data from the Korean Statistical Information Service (http://kosis.kr/; accessed on 17 May 2019), in 2017, the total population of South Korea was 51.42 million, with 357,771 births. Based on the carrier frequency in this study, the number of carriers was estimated to be 0.94 million in total, and 6,547 in newborns per year. Thus, the estimated incidence rate of SMA due to
With the development of drugs for the treatment of SMA, the need for newborn or carrier screening for the early diagnosis of SMA has become important. The US Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children recommends the addition of SMA screening to default newborn screening programs (https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp/index.html), and the American College of Medical Genetics and the American College of Obstetricians and Gynecologists recommend routine SMA carrier screening [19,20]. Cost-effectiveness analyses of SMA screening have been reported. Little, et al. [4] reported that although universal prenatal screening for SMA is not cost-effective, screening of high-risk populations, such as those with a family history, may be. Zhang, et al. [5] reported that while SMA-only preconception carrier screening is not cost-effective, a combination screen for other conditions, such as cystic fibrosis and fragile X syndrome may prove to be and may prevent up to 30 SMA patients per million (all adults between the ages of 18 and 25 in the Australian health care system). Since the approval of nusinersen, there has been a lack of cost-effective analyses for newborn or carrier screening of SMA. Therefore, large-scale prospective newborn or carrier screening studies are needed for predicting the efficacy of nusinersen treatment.
Our study had some limitations. First, while 5% of SMA patients are known to have
Our data indicate that carriers of
Distribution of