title: Modification of phenotype by SMN2 copy numbers in two Chinese families with SMN1 deletion in two continuous generations.
abstract: BACKGROUND
  As a lethal autosomal recessive hereditary disorder, childhood spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene. Most of the patients died at early stage or were seriously disabled, which accounts partly for the scarcity of two continuous generations with SMA. Increasing evidence indicated that SMN2 copy number was a modifier of SMA, but in majority of sporadic patients, the bias of phenotype judgments may largely reduce the accuracy of genotype-phenotype analysis.
  
  
  METHODS
  We presented two families with SMN1-deleted individuals in two continuous generations, the father and daughter of family 1 and the mother and daughter of family 2 were determined to be homozygous for the deletion of the SMN1 gene. Quantitative analysis of SMN1 and SMN2 was carried out by real-time fluorescence quantitative PCR and multiplex ligation-dependent probe amplification.
  
  
  RESULTS
  Quantitative analysis showed that the father of family 1 possessed three copies of SMN2, and his daughter had only two SMN2 copies; the slightly affected mother of family 2 had three copies of SMN2, but her sick daughter had only two copies of SMN2; we also performed prenatal prediction for family 1 and a healthy boy was born under our suggestion.
  
  
  CONCLUSIONS
  For the phenotypes of patients from different generations within the same family are obviously different, the results of a genotype-phenotype analysis may be more convincing, which strongly support the hypothesis that SMN2 is an important modifier for SMA, and SMN2 copy number should be considered in the prenatal diagnosis situation.
authors.affiliation: Department of Neurology, First Affiliated Hospital, Fujian Medical University, China. wanjinchen75@yahoo.com.cn
authors.forename: Wan-Jin
authors.initials: WJ
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Qi-Jie
authors.initials: QJ
authors.lastname: Zhang
authors.forename: Qi-Fang
authors.initials: QF
authors.lastname: Lin
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Chen
authors.forename: Xiao-Zhen
authors.initials: XZ
authors.lastname: Lin
authors.forename: Min-Ting
authors.initials: MT
authors.lastname: Lin
authors.forename: Shen-Xing
authors.initials: SX
authors.lastname: Murong
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005333:Fetus / Q000378:metabolism; D005500:Follow-Up Studies; D017353:Gene Deletion; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein