Abstract
Screening for carriers of spinal muscular atrophy (SMA) is necessary for effective clinical/prenatal diagnosis and genetic counseling. However, a population-based study of SMA prevalence in mainland China has not yet been conducted. In this study, the copy number of survival motor neuron (SMN) genes was determined in 1712 newborn cord blood samples collected from southern China and from 25 core families, which included 26 SMA patients and 44 parents, to identify SMA carriers. The results presented 13 groups with different SMN1/SMN2 ratios among 1712 newborn individuals, which corresponded to 1535 subjects with two copies of SMN1, 119 with three copies of SMN1, 17 with four copies of SMN1, and 41 with a heterozygous deletion of SMN1 exon 7. Simultaneously, two ‘2+0’ genotypes and two point mutations were found among the 44 obligate carriers in the core families, including a novel SMN1 splice-site mutation that was identified in the junction between intron 6 and exon 7 (c. 835–1G>A). These results indicated that the carrier frequency is 1/42 in the general Chinese population and that duplicated SMN1 alleles and de novo deletion mutations are present in a small number of SMA carriers. In addition, we developed and validated a new alternative screening method using a reverse dot blot assay for rapid genotyping of deletional SMA. Our research elucidated the genetic load and SMN gene variants that are present in the Chinese population, and could serve as the basis for a nationwide program of genetic counseling and clinical/prenatal diagnosis to prevent SMA in China.
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Acknowledgements
We sincerely thank Dr Yi-Ning Su (Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan) for his help and advice with the DHPLC method and Professor Feng-hua Lan (Fuzhou General Hospital of Nanjing Military Area, Fuzhou) for providing part of the SMA core family samples. We also thank all the participants for providing samples. This work was partially supported the Ministry of Science and Technology of China for the National Key Technologies R & D Program (2006BAI05A06) and the Genetic Resource R & D Program (30771192) and by the National Science Fund for Distinguished Young Scholars (30325037).
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Sheng-Yuan, Z., Xiong, F., Chen, YJ. 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 18, 978–984 (2010). https://doi.org/10.1038/ejhg.2010.54
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DOI: https://doi.org/10.1038/ejhg.2010.54
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