Ann Lab Med.  2020 Jul;40(4):326-330. 10.3343/alm.2020.40.4.326.

Carrier Frequency of Spinal Muscular Atrophy in a Large-scale Korean Population

• Park JE
• Yun SA
• Roh EY
• Yoon JH
• Shin S
• Ki CS

• KMID: 2470330
• DOI: http://doi.org/10.3343/alm.2020.40.4.326

Abstract

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 SMN1 and SMN2 gene copies using a multiplex ligation-dependent probe amplification assay. Twenty-nine of the 1,581 newborns [1.83%; 95% confidence interval (CI), 1.25-2.66%] were SMA carriers with one copy of SMN1, and no homozygous SMN1 deletion was detected. The carrier frequency in this population was estimated to be 1,834 per 100,000 (95% CI, 1,254-2,659) or 1 in 55 (95% CI, 1/79-1/38). Our data indicate that SMA carriers are not uncommon in the Korean population and may serve as a reference for designing a population screening program in Korea.

Keyword

Korea; Spinal muscular atrophy; Carrier frequency; multiplex ligation-dependent probe amplification

MeSH Terms

Anonyms and Pseudonyms
Atrophy
DNA
Fetal Blood
Humans
Infant, Newborn
Korea
Mass Screening
Multiplex Polymerase Chain Reaction
Muscle Weakness
Muscular Atrophy, Spinal*
DNA

Figure

• 

  Fig. 1 Distribution of SMN1 and SMN2 copy numbers. Each bar represents the percentage of SMN1 and SMN2 copy numbers in the 1,581 umbilical cord blood samples of newborns included in this study. *One newborn was suspected as a SMN1 silent (2+0) carrier.

Reference

1. Prior TW, Leach ME, Finanger E. Spinal Muscular Atrophy. 2000. In : Adam MP, Ardinger HH, Pagon RA, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle;1993–2020. Updated on Nov 2019. https://www.ncbi.nlm.nih.gov/books/NBK1352/.

2. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008; 371:2120–2133.

3. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017; 377:1723–1732.

4. Little SE, Janakiraman V, Kaimal A, Musci T, Ecker J, Caughey AB. The cost-effectiveness of prenatal screening for spinal muscular atrophy. Am J Obstet Gynecol. 2010; 202:253.e1–253.e7.

5. Zhang L, Bao Y, Riaz M, Tiller J, Liew D, Zhuang X, et al. Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis. Genet Med. 2019; 21:1958–1968.

6. Yoon S, Lee CH, Lee KA. Determination of SMN1 and SMN2 copy numbers in a Korean population using multiplex ligation-dependent probe amplification. Korean J Lab Med. 2010; 30:93–96.

7. Lee TM, Kim SW, Lee KS, Jin HS, Koo SK, Jo I, et al. Quantitative analysis of SMN1 gene and estimation of SMN1 deletion carrier frequency in Korean population based on real-time PCR. J Korean Med Sci. 2004; 19:870–873.

8. Luo M, Liu L, Peter I, Zhu J, Scott SA, Zhao G, et al. An Ashkenazi Jewish SMN1 haplotype specific to duplication alleles improves pan-ethnic carrier screening for spinal muscular atrophy. Genet Med. 2014; 16:149–156.

9. Verhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy–a literature review. Orphanet J Rare Dis. 2017; 12:124.

10. Chan V, Yip B, Yam I, Au P, Lin CK, Wong V, et al. Carrier incidence for spinal muscular atrophy in southern Chinese. J Neurol. 2004; 251:1089–1093.

11. Sheng-Yuan Z, Xiong F, Chen YJ, Yan TZ, Zeng J, Li L, et al. Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population. Eur J Hum Genet. 2010; 18:978–984.

12. Qu XX, Xiao B, Ji X, Jiang WT, Yang ZJ, Tao J. A pilot study on spinal muscular atrophy carrier screening in Shanghai region using real-time PCR. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013; 30:1–4.

13. Gong B, Zhang L, Hou YP, Hu HY, Li HC, Tan MY, et al. Carrier screening for spinal muscular atrophy in 4719 pregnant women in Shanghai region. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013; 30:670–672.

14. Tan J, Zhang X, Wang Y, Luo S, Yang F, Liu B, et al. Screening for spinal muscular atrophy mutation carriers among 4931 pregnant women from Liuzhou region of Guangxi. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018; 35:467–470.

15. Huang CH, Chang YY, Chen CH, Kuo YS, Hwu WL, Gerdes T, et al. Copy number analysis of survival motor neuron genes by multiplex ligation-dependent probe amplification. Genet Med. 2007; 9:241–248.

16. Chen TH, Tzeng CC, Wang CC, Wu SM, Chang JG, Yang SN, et al. Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population. J Neurol Sci. 2011; 308:83–87.

17. Su YN, Hung CC, Lin SY, Chen FY, Chern JP, Tsai C, et al. Carrier screening for spinal muscular atrophy (SMA) in 107,611 pregnant women during the period 2005-2009: a prospective population-based cohort study. PLoS One. 2011; 6:e17067.

18. Wang KC, Chang CC, Chang YF, Wang SH, Chiang CK, Tsai CP. Evaluation and characterization of a high-resolution melting analysis kit for rapid carrier-screening test of spinal muscular atrophy. J Neurogenet. 2015; 29:113–116.

19. Prior TW. Professional Practice and Guidelines Committee. Carrier screening for spinal muscular atrophy. Genet Med. 2008; 10:840–842.

20. Committee Opinion No. 691. Committee Opinion No. 691: Carrier screening for genetic conditions. Obstet Gynecol. 2017; 129:e41–e55.