title: SMN1 dosage analysis in spinal muscular atrophy from India.
abstract: BACKGROUND
  Spinal muscular atrophy (SMA) represents the second most common fatal autosomal recessive disorder after cystic fibrosis. Due to the high carrier frequency, the burden of this genetic disorder is very heavy in developing countries like India. As there is no cure or effective treatment, genetic counseling becomes very important in disease management. SMN1 dosage analysis results can be utilized for identifying carriers before offering prenatal diagnosis in the context of genetic counseling.
  
  
  METHODS
  In the present study we analyzed the carrier status of parents and sibs of proven SMA patients. In addition, SMN1 copy number was determined in suspected SMA patients and parents of children with a clinical diagnosis of SMA.
  
  
  RESULTS
  Twenty nine DNA samples were analyzed by quantitative PCR to determine the number of SMN1 gene copies present, and 17 of these were found to have one SMN1 gene copy. The parents of confirmed SMA patients were found to be obligate carriers of the disease. Dosage analysis was useful in ruling out clinical suspicion of SMA in four patients. In a family with history of a deceased floppy infant and two abortions, both parents were found to be carriers of SMA and prenatal diagnosis could be offered in future pregnancies.
  
  
  CONCLUSIONS
  SMN1 copy number analysis is an important parameter for identification of couples at risk for having a child affected with SMA and reduces unwarranted prenatal diagnosis for SMA. The dosage analysis is also useful for the counseling of clinically suspected SMA with a negative diagnostic SMA test.
authors.affiliation: Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-14, U,P, India. akanshapgi@yahoo.com
authors.forename: Akanchha
authors.initials: A
authors.lastname: Kesari
authors.forename: Hanna
authors.initials: H
authors.lastname: Rennert
authors.forename: Debra G B
authors.initials: DG
authors.lastname: Leonard
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D002648:Child; D002872:Chromosome Deletion; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D018628:Gene Dosage; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein