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

OBJECTIVES

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 ( gene) is cause of this disease. The purpose of present study was to investigate disease-causing mutations on 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, 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 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 protein was predicted using study.

CONCLUSION

The causative mutation in studied patient with SMED was identified using Next-generation sequencing (NGS), successfully. The identified novel mutation in gene can be useful in prenatal diagnosis (PND) of SMED, preimplantation genetic diagnosis (PGD), and genetic counseling.