Mutations in DDR2 Gene Cause SMED with Short Limbs and Abnormal Calcifications

Ruth Bargal, Valerie Cormier-Daire, Ziva Ben-Neriah, Martine Le Merrer, Jacob Sosna, Judith Melki, David H. Zangen, Sarah F. Smithson, Zvi Borochowitz, Ruth Belostotsky, Annick Raas-Rothschild*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)80-84
Number of pages5
JournalAmerican Journal of Human Genetics
Volume84
Issue number1
DOIs
StatePublished - 9 Jan 2009
Externally publishedYes

Bibliographical note

Funding 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.

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