Birth Defects Res A Clin Mol Teratol 2013 Dec 6;97(12):764-9. Epub 2013 Sep 6.
Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University.
Background: Geleophysic dysplasia (GD) is an autosomal recessive disorder characterized by short stature, brachydactyly, stiff joints, thick skin, and cardiac valvular abnormalities that are often responsible for early death. Mutations in ADAMTSL2 and FBN1 genes have been shown to cause GD due to the dysregulation of transforming growth factor-β signaling pathways. Small numbers of mutations in ADAMTSL2 have been reported so far in patients with GD type 1 (GD1).
Methods: In this study, we clinically evaluated two children from two consanguineous Arab families living in the United Arab Emirates with GD1. In addition we have sequenced all the coding exons of ADAMTSL2 gene using Sanger sequencing.
Results: The two patients exhibited most of the typical features of this rare bone dysplasia. Molecular analysis of the ADAMTSL2 gene revealed two novel homozygous missense mutations (c.938T>C, p.M313T and c.499G>A, p.D167N). The mutations segregated well in the studied families with the parents being heterozygous. In addition, bioinformatics analyses showed that these mutations are affecting conserved amino acids residues and thus strongly support their pathogenicity.
Conclusion: We describe the clinical phenotypes of two patients with GD1 that are caused by two novel homozygous missense mutations in the ADAMTSL2 gene.