• Identification of mutations in the OFD1 gene among Lorestani families
  • Hamed Esmaeil Lashgarian ,1 Hamidreza Khodadadi ,2,* Masumeh Jalalvand ,3 Maryam Zand ,4 Amirmasoud Jalalvand ,5 leila Abkhooie ,6
    1. Associate Professor, Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
    2. Assistant Professor, Hepatitis Research Center, Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
    3. Assistant Professor, Hepatitis Research Center, Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
    4. Department of Biotechnology and Molecular Medicine, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
    5. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
    6. Assistant Professor, Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran


  • Introduction: This study aimed to investigate the presence of mutations in the OFD1 gene among individuals from Lorestan, a region with a high prevalence of certain genetic disorders. The OFD1 gene is known to be associated with Oral-Facial-Digital syndrome type I (OFD1), a rare genetic condition characterized by a range of clinical features including oral, facial, and digital abnormalities. Despite the identification of various mutations in the OFD1 gene in different populations, this study represents the first report of a missense mutation in the Lorestani population, highlighting the genetic diversity and the need for targeted genetic screening in this region.
  • Methods: Genomic DNA was extracted from the blood sample. Whole Genome Sequencing was performed, and the results were confirmed by Sanger sequencing. In silico tools such as Provean web server was utilized to predict the functional effect of amino acid substitutions. I-Mutant was used to calculate the change in Gibbs' free energy (ΔΔG) and assess OFD1.
  • Results: Exome sequencing demonstrated a missense mutation c.1397C>G, p.A466G in exon 14 of the OFD1 gene in Lorestani families. Sanger sequencing confirmed this Missense variant in the OFD1 gene. According to Provean web server web server analysis, p.A466G mutation in OFD1 can be classified as a deleterious mutation with Provean score of approximately -2. 580. The I-Mutant analysis demonstrated a ΔΔG value of -1.70, indicating a significant reduction in protein stability.
  • Conclusion: The identification of the c.1397C>G missense mutation in the OFD1 gene in Lorestani families, confirmed by Sanger sequencing, and characterized as deleterious by in silico analyses, underscores the importance of genetic screening in populations with a high prevalence of OFD1 syndrome. The significant reduction in protein stability predicted by I-Mutant, along with the deleterious classification by Provean, suggests that this mutation may contribute to the clinical manifestations of OFD1 syndrome in the affected individuals. These findings expand the spectrum of known OFD1 mutations and provide valuable insights into the genetic basis of OFD1 syndrome in the Lorestani population, which could inform future diagnostic and therapeutic strategies.
  • Keywords: missense mutation, OFD1, In silico tools