Identification of a novel homozygous mutation in the DDR2 gene from a patient with spondylo-meta-epiphyseal dysplasia by whole exome sequencing

Document Type : Original Article

Authors

1 Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

2 Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran

3 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

4 Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences (TUMS), Tehran, Iran

5 Department of Medical Genetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran

Abstract

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.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 2
February 2021
Pages 191-195

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