title: Molecular analysis of the SMN1 and NAIP genes in Iranian patients with spinal muscular atrophy.
abstract: BACKGROUND
  Childhood-onset proximal spinal muscular atrophies (SMAs) are an autosomal recessive, clinically heterogeneous group of neuropathies characterised by the selective degeneration of anterior horn cells. SMA has an estimated incidence of 1 in 10,000 live births. The causative genes are survival motor neuron (SMN) gene and neuronal apoptosis inhibitory protein (NAIP) gene. Deletions of the telomeric copy of SMN gene (SMN1) have been reported in 88.5% to 95% of SMA cases, whereas the deletion rate for NAIP gene (NAIP) is between 20% and 50% depending on the disease severity. The main objective of this study was to genetically characterise the childhood onset of SMA in Iran.
  
  
  METHODS
  Molecular analysis was performed on a total of 75 patients with a clinical diagnosis of SMA. In addition to common PCR analysis for SMN1 exons 7 and 8, we analysed NAIP exons 4 and 5, along with exon 13, as a internal control, by bi-plex PCR.
  
  
  RESULTS
  The homozygous-deletion frequency rate for the telomeric copy of SMN exons 7 and 8 in all types of SMA was 97%. Moreover, exons 5 and 6 of NAIP gene were deleted in approximately 83% of all SMA types. Three deletion haplotypes were constructed by using SMN and NAIP genotypes. Haplotype A, in which both genes are deleted, was seen in approximately 83% of SMA types I and II but not type III. It was also found predominantly in phenotypically severe group with an early age of onset (i.e., less than 6-month-old). We also report 34 of our prenatal diagnosis.
  
  
  CONCLUSIONS
  To our knowledge, the present study is the first one giving detailed information on SMN and NAIP deletion rates in Iranian SMA patients. Our results show that the frequency of SMN1 homozygous deletions in Iran is in agreement with previous studies in other countries. The molecular analysis of SMA-related gene deletion/s will be a useful tool for pre- and postnatal diagnostic.
authors: Department of Medical Genetics, Medical Sciences/University of Tehran, Iran. derakhshandeh@tums.ac.ir
authors: Pupak
authors: P
authors: Derakhshandeh-Peykar
authors: Mohsen
authors: M
authors: Esmaili
authors: Zahra
authors: Z
authors: Ousati-Ashtiani
authors: Manijeh
authors: M
authors: Rahmani
authors: Farbod
authors: F
authors: Babrzadeh
authors: Shahla
authors: S
authors: Farshidi
authors: Elham
authors: E
authors: Attaran
authors: Mohammad Mehdi
authors: MM
authors: Sajedifar
authors: Dariush Daneshvar
authors: DD
authors: Farhud
mesh_terms: D017668:Age of Onset; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007492:Iran; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics*; 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; D051616:Neuronal Apoptosis-Inhibitory Protein; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein