Comprehensive copy number analysis of spinal muscular atrophy among the Iranian population

Sci Rep. 2024 Dec 2;14(1):29880. doi: 10.1038/s41598-024-76815-x.

Abstract

Copy number variations in the SMN1 gene on chromosome 5 are the primary cause of Spinal Muscular Atrophy (SMA) disease, characterized by muscle weakness and degeneration due to impaired alpha motor neurons in the spinal cord. To obtain a comprehensive molecular understanding of the SMA, including carriers, silent carriers, and patients in the Iranian population, we analyzed data from 5224 individuals referred to Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran, between 2006 and 2023 using MLPA and quantitative RT-PCR methods. The carrier frequency of SMA was estimated to be 5.55%. Furthermore, 3.06% of SMA parents (n = 24) had two copies of the SMN1 gene. Among 725 patients, those with an earlier onset of SMA were more likely to have two copies of the SMN2 gene (46.45%) and no copies of the NAIP gene (49.36%). Among the 654 fetal samples screened for SMA, 22.33% were found to be affected, while 3.46% of their parents tested normal. These findings are valuable for genetic counseling, carrier screening, and prenatal diagnosis of SMA in Iran. Furthermore, they underscore the importance of CNV analysis of SMN1, SMN2, and NAIP genes for accurate diagnosis and prognosis of SMA.

Keywords: SMN; Carrier frequency; Copy numbers; Iran; Silent carriers; Spinal muscular atrophy.

MeSH terms

  • Adult
  • DNA Copy Number Variations*
  • Female
  • Heterozygote
  • Humans
  • Iran / epidemiology
  • Male
  • Muscular Atrophy, Spinal* / epidemiology
  • Muscular Atrophy, Spinal* / genetics
  • Neuronal Apoptosis-Inhibitory Protein / genetics
  • Survival of Motor Neuron 1 Protein* / genetics
  • Survival of Motor Neuron 2 Protein* / genetics

Substances

  • Survival of Motor Neuron 1 Protein
  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 2 Protein
  • Neuronal Apoptosis-Inhibitory Protein
  • NAIP protein, human