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

Abstract : Purpose Based on prenatal suspicion of the combination of radioulnar or radiohumeral synostosis and a peculiar shape of the skull suggestive of craniosynostosis, we report on six patients from four unrelated consanguineous families in whom Antley-Bixler syndrome was suspected during the prenatal period without mutation in genes known to be associated with the syndrome. Methods Molecular diagnosis involved whole-exome and gene-panel sequencing. Results: 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. Conclusion We 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.
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https://hal.archives-ouvertes.fr/hal-01634463
Contributor : Lnc - Université de Bourgogne <>
Submitted on : Tuesday, November 14, 2017 - 10:41:43 AM
Last modification on : Tuesday, February 25, 2020 - 4:10:03 PM

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Kevin Yauy, Frederic Tran Mau-Them, Marjolaine Willems, Christine Coubes, Patricia Blanchet, et al.. B3GAT3-related disorder with craniosynostosis and bone fragility due to a unique mutation. Genetics in Medicine, Nature Publishing Group, 2018, 20 (2), pp.269-274. ⟨10.1038/gim.2017.109⟩. ⟨hal-01634463⟩

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