B3GAT3-related disorder with craniosynostosis and bone fragility due to a unique mutation

Abstract

All sequenced patients showed a unique homozygous mutation of c.667G>A, p.Gly223Ser (NM_012200) in the beta-1,3-glucuronyltransferase 3 (B3GAT3) gene known to be involved in linkeropathy syndrome. Linkeropathies correspond to a recently identified group of heterogeneous genetic syndromes along a spectrum of skeletal and connective tissue disorders. These patients featured mainly craniosynostosis, midface hypoplasia, bilateral radioulnar synostosis, multiple neonatal fractures, dislocated joints, joint contracture, long fingers, foot deformity, and cardiovascular abnormalities. All died before 1 year of age.ConclusionWe identified a novel B3GAT3-related disorder with craniosynostosis and bone fragility, due to a unique homozygous mutation in B3GAT3. This syndrome should be considered in the prenatal period in light of the severe outcome and as an alternative diagnosis to Antley-Bixler or Shprintzen-Goldberg syndrome.

Bone and connective tissue disorders caused by defects in glycosaminoglycan biosynthesis: a panoramic view

“…Because the patient's phenotype was more severe than that reported for other patients with mutations in B3GAT3, the authors performed exome sequencing, but did not find any additional causative mutation [73]. Similar features with bone fragility and severe osteopenia have been reported recently by Yauy et al [74]. Alazami et al reported a gerodermia osteodysplastica-like phenotype in a patient with a homozygous missense mutation in B3GAT3 (c.245C>T, p.Pro82Leu) [75].…”

“…Similar features with bone fragility and severe osteopenia have been reported recently by Yauy et al . . Alazami et al .…”

Genetic Causes of Craniosynostosis: An Update

“…In 6 patients from 4 unrelated consanguineous families, a unique homozygous mutation in the B3GAT3 gene was identified [Yauy et al, 2018]. During the prenatal period, Antley-Bixler syndrome was clinically suspected [Yauy et al, 2018].…”

“…During the prenatal period, Antley-Bixler syndrome was clinically suspected [Yauy et al, 2018]. The patients had craniosynostosis, midface hypoplasia, bilateral radioulnar synostosis, multiple neonatal fractures, dislocated joints, joint contracture, long fingers, foot deformities, and cardiovascular abnormalities [Yauy et al, 2018].…”

“…The patients had craniosynostosis, midface hypoplasia, bilateral radioulnar synostosis, multiple neonatal fractures, dislocated joints, joint contracture, long fingers, foot deformities, and cardiovascular abnormalities [Yauy et al, 2018]. All patients died before 1 year of age [Yauy et al, 2018]. Homozygous mutations in B3GAT3 have been described as linkeropathies [Bloor et al, 2017].…”