title: Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.
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.
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Sheng-Yuan
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ti-Zhen
authors.initials: TZ
authors.lastname: Yan
authors.forename: Jian
authors.initials: J
authors.lastname: Zeng
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Zhang
authors.forename: Wan-Qun
authors.initials: WQ
authors.lastname: Chen
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Bao
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Xu
mesh_terms: D001483:Base Sequence; D002681:China; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D009154:Mutation; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: D017931:DNA Primers; D055533:Survival of Motor Neuron 1 Protein