Masoud Heidari - Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
Morteza Soleyman-Nejad - Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran
Alireza Isazadeh - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Mohammad Hossein Taskiri - Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran
Manzar Bolhassani - Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran
Nahid Sadighi - Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences (TUMS), Tehran, Iran
Zahra Shiri - Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran
Zahra Karimi - Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran
Mansour Heidari - Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran

Objective(s): The spondylo-meta-epiphyseal dysplasia (SMED) short limbs-hand type is a rare autosomal recessive disease, which is characterized by premature calcification leading to severe disproportionate short stature and various skeletal changes. Defective function of a conserved region encoding discoidin domain receptor tyrosine kinase 2 (DDR2 protein) by the discoidin domain-containing receptor 2 (DDR2 gene) is cause of this disease. The purpose of present study was to investigate disease-causing mutations on DDR2 gene in an Iranian family with SMED, and predict the DDR2 protein molecular mechanism in development of SMED.Materials and Methods: In the present study, we evaluated a 2-year-old male with SMED. Detection of genetic changes in the studied patient was performed using Whole-Exome Sequencing (WES). PCR direct sequencing was performed for analysis of co-segregation of variants with the disease in family. Finally, in silico study was performed for further identification of molecular function of the identified genetic variant.Results: We detected a novel splice-site mutation (NM_001014796: exon9: c.855+1G>A; NM_006182: exon8: c.855+1G>A) in DDR2 gene of the studied patient using WES. This mutation was exclusively detected in patients with homozygous SMED, not in healthy people. The effects of detected mutation on functions of DDR2 protein was predicted using in silico study.Conclusion: The causative mutation in studied patient with SMED was identified using Next-generation sequencing (NGS), successfully. The identified novel mutation in DDR2 gene can be useful in prenatal diagnosis (PND) of SMED, preimplantation genetic diagnosis (PGD), and genetic counseling.

DDR2 gene In silico Sanger sequencing Splice, site mutation Spondylo, meta, epiphyseal dysplasia Whole exome sequencing