Bone Abstracts

Proteoglycans are abundant and structurally complex bio macromolecules. They reside on the cell surface and are a major component of the extracellular matrix including bone. Defective formation of proteoglycans may case pleiotropic connective tissue syndromes including EDS-like and Larsen syndrome–like phenotypes.

We report on a girl with disproportionate short stature and joint laxity with pes planus and radial head dislocation. She was previously assigned to Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) which is characterized by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis, thoracic asymmetry, and respiratory compromise resulting in early death. The phenotype was similar, but except atlantoaxial hypermobility she did not develop scoliosis. This prompted us to Whole-Exom-Sequencing for a recessive mutation in a consanguineous mating. Nonaxial skeletal involvement included elbow deformities with radial head dislocation, genu valgum, flat feet, and tapered fingers with spatulate distal phalanges. The girl had a round face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Decreased bone density was reported in most of the patients

Final height was 130 cm (−5.3 SDS),weight 37 kg (<3^rd centile), normal cognitive function.

Whole Exome Sequencing by SOLID 5500 (ThermoFIsher) revealed a homozygous missense mutation in B3GAT3-gene coding for Glucoronyl-transferase I (enzymatic step in the Golgi apparatus for a linkage region synthesis of proteoglycans i.e heparan sulfate): c.416C>T, p.Thr139Met. This residue is highly conserved and predicted as pathogenic by Polyphen-2 and MutationTaster.

We add an additional patient to a group of patients with short stature and joint laxity caused by mutations in the linker region of glycosaminoglycans (GAG) including syndromes with mutation in B3GAT3, B3GALT6 (Ehlers-Danlos- like), B4GALT6 (Ehlers-Danlos-like syndrome with kyphoskoliosis), B4GALT7 (Larsen of Reunion Island Syndrome).

Disclosure: The authors declared no competing interests.