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neurogenetics

, Volume 16, Issue 4, pp 299–306 | Cite as

In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous Pakistani family showing amyotrophic lateral sclerosis without frontotemporal lobar dementia

  • Muhammad Ikram Ullah
  • Arsalan Ahmad
  • Syed Irfan Raza
  • Ali Amar
  • Amjad Ali
  • Attya Bhatti
  • Peter John
  • Aisha Mohyuddin
  • Wasim Ahmad
  • Muhammad Jawad HassanEmail author
Original Article

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. It has been found to be associated with frontotemporal lobar degeneration (FTLD). In the present study, we have described homozygosity mapping and gene sequencing in a consanguineous autosomal recessive Pakistani family showing non-juvenile ALS without signs of FTLD. Gene mapping was carried out in all recruited family members using microsatellite markers, and linkage was established with sigma non-opioid intracellular receptor 1 (SIGMAR1) gene at chromosome 9p13.2. Gene sequencing of SIGMAR1 revealed a novel 3′-UTR nucleotide variation c.672*31A>G (rs4879809) segregating with disease in this family. The C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls. In silico analysis was carried out to explore the possible role of 3′-UTR variant of SIGMAR1 in ALS. The Regulatory RNA motif and Element Finder program revealed disturbance in miRNA (hsa-miR-1205) binding site due to this variation. ESEFinder analysis showed new SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores due to this variation. Our results indicate that the 3′-UTR SIGMAR1 variant c.672*31A>G may have a role in the pathogenesis of ALS in this family.

Keywords

ALS SIGMAR1 3′-UTR Pakistan 

Notes

Acknowledgments

We are grateful to the family members for cooperating in the research process.

Conflict of interest

All authors declare no competing interests.

Supplementary material

10048_2015_453_MOESM1_ESM.xls (20 kb)
Supplementary Table 1 (XLS 19 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Muhammad Ikram Ullah
    • 1
    • 2
  • Arsalan Ahmad
    • 3
  • Syed Irfan Raza
    • 1
  • Ali Amar
    • 4
  • Amjad Ali
    • 5
  • Attya Bhatti
    • 5
  • Peter John
    • 5
  • Aisha Mohyuddin
    • 6
  • Wasim Ahmad
    • 1
  • Muhammad Jawad Hassan
    • 5
    Email author
  1. 1.Department of Biochemistry, Faculty of Biological SciencesQuaid i Azam UniversityIslamabadPakistan
  2. 2.PCR and Research Laboratories, Shifa College of MedicineShifa Tameer e Millat UniversityIslamabadPakistan
  3. 3.Division of Neurology, Shifa College of Medicine, Shifa International HospitalShifa Tameer e Millat UniversityIslamabadPakistan
  4. 4.Department of Human Genetics and Molecular BiologyUniversity of Health SciencesLahorePakistan
  5. 5.Atta ur Rahman School of Applied Biosciences (ASAB)National University of Sciences & Technology (NUST)IslamabadPakistan
  6. 6.Section of Biochemistry, Shifa College of MedicineShifa Tameer e Millat University (STMU)IslamabadPakistan

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