Discoidin Domain Receptor Family, Member 2 gene encodes for discoidin domain receptors (DDR2), it consists of 855 amino acids and weighs about 97 kDa. DDR2 is a member of the subfamily of receptor tyrosine kinases (RTKs) that regulate cell differentiation, remodeling of the extracellular matrix, cell migration, and cell proliferation. DDR2 is found on cells of mesenchymal origin, and it functions in human skeletal growth.
The DDR2 gene is mapped to chromosome 1q23.3, and it is only about 3 kb long with 19 exons. Mutation in the DDR2 gene is found to be responsible for Spondylometaepiphyseal Dysplasia, Short Limb-Hand Type disorder (SEMD-SL). Four mutations in the DDR2 gene have been identified in people affected with SEMD-SL disorder; three of them were missense mutations c.C2254T (p.R752C), c.T2177G (p.I726R), and c.C2138T (p.T713I), while one was a splice site mutation IVS17 G>A, +1 resulting in skipping exon 17.
[See: Palestine > Bargal et al., 2009].
Al-Gazali et al. (1996) described the clinical characteristics of a consanguineous Egyptian family living in the UAE and suffering from SEMD-SL disorder. In 2010, Ali et al. (2010) studied the molecular basis of SEMD-SL disorder in the same family. A homozygous c.C2254T missense mutation was found in the two affected children in exon 17 of the DDR2 gene, resulting in an arg752cys (p.R752C) substitution, while both parents were heterozygous for this mutation. This mutation is located in the DDR2 intracellular domain.
Bargal et al. (2009) studied six patients with SMED-SL belonging to five unrelated Arab Muslim families from the Jerusalem area. Homozygosity mapping on these and another affected patient from Algeria identified a 2.4 Mb candidate region on chromosome 1q, which included the DDR2 gene. Sequencing of this gene identified a single missesnse mutation c.2254C>T (p.R752C), in all six patients from Jerusalem and another missense mutation, c.2177 T>G (p.I726R), in an Algerian patient.
[See: Egypt > Al-Gazali et al. 1996; Ali et al., 2010].