title: Gene dosage analysis of proximal spinal muscular atrophy carriers using real-time PCR.
abstract: BACKGROUND
  Autosomal recessive spinal muscular atrophy is a disease resulting from homozygous absence of SMN1 gene in approximately 94% of SMA patients. To identify patients who retained a single SMN1 copy, SMN1 dosage analysis was performed by quantitative Real-time PCR using SYBR green dye. SMN1 dosage analysis results were utilized to identify carriers before offering prenatal diagnosis.
  
  
  METHODS
  Carrier testing was performed for 150 individuals. Copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and human serum albumin gene was used as a reference.
  
  
  RESULTS
  Analysis of 150 DNA samples with quantitative PCR determined the number of SMN1 gene copies. Of these, 50 (33.33%) cases had one SMN1 gene copy, 87 (58%) had two copies and 13 (8.66%) did not have any copies of SMN1. The homozygous SMN1 deletion ratio was 0.00 and deletion of one copy of SMN1 gene ratio ranged from 0.3 to 0.58.
  
  
  CONCLUSIONS
  This report demonstrates modification of risk estimation for the diagnosis and detection of SMA carriers by accurate determination of SMN1 copy number. SMN1 copy number analysis is an important parameter for identification of couples at risk of having children affected with SMA. It also reduces unwarranted prenatal diagnosis for SMA. Furthermore, the dosage analysis might be useful for the counseling of clinically suspected SMA patients with negative diagnostic SMA tests.
authors.affiliation: Pardis Clinical and Genetics Laboratory, Mashhad, Iran. abbaszadegsnmr@mums.ac.ir
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Abbaszadegan
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Keify
authors.forename: Farah
authors.initials: F
authors.lastname: Ashrafzadeh
authors.forename: Moein
authors.initials: M
authors.lastname: Farshchian
authors.forename: Farhad
authors.initials: F
authors.lastname: Khadivi-Zand
authors.forename: Mohammad Naser
authors.initials: MN
authors.lastname: Teymoorzadeh
authors.forename: Faezeh
authors.initials: F
authors.lastname: Mojahedi
authors.forename: Reza
authors.initials: R
authors.lastname: Ebrahimzadeh
authors.forename: Mitra
authors.initials: M
authors.lastname: Ahadian
mesh_terms: D017353:Gene Deletion; D018628:Gene Dosage; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D060888:Real-Time Polymerase Chain Reaction; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein