The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a rare autosomal-recessive disease, first reported by Borochowitz et al. in 1993.1 Since then, 14 affected patients have been reported.2-5 We diagnosed 6 patients from 5 different consanguineous Arab Muslim families from the Jerusalem area with SMED-SL. Additionally, we studied two patients from Algerian and Pakistani ancestry and the parents of the first Jewish patients reported.1 Using a homozygosity mapping strategy, we located a candidate region on chromosome 1q23 spanning 2.4 Mb. The position of the Discoidin Domain Receptor 2 (DDR2) gene within the candidate region and the similarity of the ddr2 knockout mouse to the SMED patients' phenotype prompted us to study this gene6. We identified three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R], c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene. The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk.
Bibliographical noteFunding Information:
We are grateful to the families for their participation in this study; we wish to thank Professor Orly Elpeleg for her help with computational SNP analysis and Dr. Mira Korner of the National Center of Genomic Technologies at the Hebrew University of Jerusalem for the SNP analysis. We thank Dr. Zeev Paroush for his fruitful comments and support. This research was supported by a grant provided by the Z. family.