Analysis of Spinal Muscular Atrophy Carrier Screening Results in 32,416 Pregnant Women and 7,231 Prepregnant Women

Overview

Journal Front Neurol

Specialty Neurology

Date 2024 Apr 24

PMID 38654739

Authors

Bing-Bo Zhou

Xue Chen

Chuan Zhang

Yu-Pei Wang

Pan-Pan Ma

Sheng-Ju Hao

Ling Hui

Yun-Fei Bai

Affiliations

Soon will be listed here.

Abstract

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA.

Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects. To validate the accuracy of our findings, we also utilized the Multiplex Ligation-dependent Probe Amplification (MLPA) to confirm the reliability of screening results obtained by quantitative real-time PCR.

Result: Among the 39,647 participants who were screened, 726 participants were the carriers of . The overall carrier rate was calculated to be 1.83% (95% confidence interval: 0.86-2.8%). After undergoing screening, a total of 592 pregnancy carriers were provided with genetic counseling and only 503 of their spouses (84.97, 95% confidence interval: 82.09-87.85%) voluntarily underwent SMA screening.

Conclusion: This study provides crucial insights into the prevalence and distribution of SMA carriers among the female population. The identification of 726 asymptomatic carriers highlights the necessity of comprehensive screening programs to identify at-risk individuals and ensure appropriate interventions are in place to minimize the impact of SMA-related conditions.

Citing Articles

Saliva Sample-Based Non-Invasive Carrier Screening for Spinal Muscular Atrophy, Hereditary Hearing Loss, and Thalassemia in 13,926 Women of Reproductive Age From South Zhejiang.

Xu C, Xiang Y, Lin X, Ma Q, Xu Y, Li H Mol Genet Genomic Med. 2025; 13(2):e70064.

PMID: 39988971 PMC: 11847965. DOI: 10.1002/mgg3.70064.

References

Gong B, Zhang L, Hou Y, Hu H, Li H, Tan M . [Carrier screening for spinal muscular atrophy in 4719 pregnant women in Shanghai region]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013; 30(6):670-2. DOI: 10.3760/cma.j.issn.1003-9406.2013.06.008. View

Nilay M, Moirangthem A, Saxena D, Mandal K, Phadke S . Carrier frequency of SMN1-related spinal muscular atrophy in north Indian population: The need for population based screening program. Am J Med Genet A. 2020; 185(1):274-277. DOI: 10.1002/ajmg.a.61918. View

Gilliam T, Brzustowicz L, Castilla L, Lehner T, Penchaszadeh G, Daniels R . Genetic homogeneity between acute and chronic forms of spinal muscular atrophy. Nature. 1990; 345(6278):823-5. DOI: 10.1038/345823a0. View

Sypniewski M, Kresa D, Dobosz P, Topolski P, Kotula L, Sztromwasser P . Population WGS-based spinal muscular atrophy carrier screening in a cohort of 1076 healthy Polish individuals. J Appl Genet. 2022; 64(1):135-139. DOI: 10.1007/s13353-022-00737-5. View

Zhao S, Wang W, Wang Y, Han R, Fan C, Ni P . NGS-based spinal muscular atrophy carrier screening of 10,585 diverse couples in China: a pan-ethnic study. Eur J Hum Genet. 2020; 29(1):194-204. PMC: 7852551. DOI: 10.1038/s41431-020-00714-8. View

Huang Z, Yang Q, Ye J, Huang J, Lin J, Chen J . Screening and prenatal diagnosis of survival motor neuron gene deletion in pregnant women in Zhaoqing city, Guangdong Province. BMC Med Genomics. 2023; 16(1):39. PMC: 9976494. DOI: 10.1186/s12920-023-01468-0. View

Su Y, Hung C, Lin S, Chen F, Chern J, Tsai C . 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(2):e17067. PMC: 3045421. DOI: 10.1371/journal.pone.0017067. View

Prior T, Nagan N, Sugarman E, Batish S, Braastad C . Technical standards and guidelines for spinal muscular atrophy testing. Genet Med. 2011; 13(7):686-94. DOI: 10.1097/GIM.0b013e318220d523. View

Zerres K, Rudnik-Schoneborn S . Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. 1995; 52(5):518-23. DOI: 10.1001/archneur.1995.00540290108025. View

10.

Sugarman E, Nagan N, Zhu H, Akmaev V, Zhou Z, Rohlfs E . Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2011; 20(1):27-32. PMC: 3234503. DOI: 10.1038/ejhg.2011.134. View

11.

Shum B, Henner I, Cairns A, Pretorius C, Wilgen U, Barahona P . Technical feasibility of newborn screening for spinal muscular atrophy by next-generation DNA sequencing. Front Genet. 2023; 14:1095600. PMC: 9878289. DOI: 10.3389/fgene.2023.1095600. View

12.

Tan J, Zhang X, Wang Y, Luo S, Yang F, Liu B . [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(4):467-470. DOI: 10.3760/cma.j.issn.1003-9406.2018.04.001. View

13.

Archibald A, Smith M, Burgess T, Scarff K, Elliott J, Hunt C . Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests. Genet Med. 2017; 20(5):513-523. DOI: 10.1038/gim.2017.134. View

14.

Mercuri E, Finkel R, Muntoni F, Wirth B, Montes J, Main M . Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018; 28(2):103-115. DOI: 10.1016/j.nmd.2017.11.005. View

15.

Jedrzejowska M, Milewski M, Zimowski J, Zagozdzon P, Kostera-Pruszczyk A, Borkowska J . Incidence of spinal muscular atrophy in Poland--more frequent than predicted?. Neuroepidemiology. 2010; 34(3):152-7. DOI: 10.1159/000275492. View

16.

Gao S, Wu D, Liu S, Shen Y, Zhao Z, Wang Y . Detection of male 2+0 and 1+0 carriers for spinal muscular atrophy by digital PCR. Clin Genet. 2023; 104(1):90-99. DOI: 10.1111/cge.14342. View

17.

Zhang J, Wang Y, Ma D, Sun Y, Li Y, Yang P . Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in 13,069 Chinese Pregnant Women. J Mol Diagn. 2020; 22(6):817-822. DOI: 10.1016/j.jmoldx.2020.03.001. View

18.

Tan J, Zhang J, Sun R, Jiang Z, Wang Y, Ma D . Evaluating the performance of four assays for carrier screening of spinal muscular atrophy. Clin Chim Acta. 2023; 548:117496. DOI: 10.1016/j.cca.2023.117496. View

19.

Vezain M, Thauvin-Robinet C, Vial Y, Coutant S, Drunat S, Urtizberea J . Retrotransposon insertion as a novel mutational cause of spinal muscular atrophy. Hum Genet. 2022; 142(1):125-138. DOI: 10.1007/s00439-022-02473-6. View

20.

Chen X, Sanchis-Juan A, French C, Connell A, Delon I, Kingsbury Z . Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data. Genet Med. 2020; 22(5):945-953. PMC: 7200598. DOI: 10.1038/s41436-020-0754-0. View