Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia
Description
Background Acromelic dysplasias are a group of disorders characterised by short stature, brachydactyly, limited joint extension and thickened skin and comprises acromicric dysplasia (AD), geleophysic dysplasia (GD), Myhre syndrome and Weill–Marchesani syndrome. Mutations in several genes have been identified for these disorders (including latent transforming growth factor β (TGF-β)-binding protein-2 (LTBP2), ADAMTS10, ADAMSTS17 and fibrillin-1 (FBN1) for Weill–Marchesani syndrome, ADAMTSL2 for recessive GD and FBN1 for AD and dominant GD), encoding proteins involved in the microfibrillar network. However, not all cases have mutations in these genes. Methods Individuals negative for mutations in known acromelic dysplasia genes underwent whole exome sequencing. Results A heterozygous missense mutation (exon 14: c.2087C>G: p.Ser696Cys) in latent transforming growth factor β (TGF-β)-binding protein-3 (LTBP3) was identified in a dominant AD family. Two distinct de novo heterozygous LTPB3 mutations were also identified in two unrelated GD individuals who had died in early childhood from respiratory failure–a donor splice site mutation (exon 12 c.1846+5G>A) and a stop-loss mutation (exon 28: c.3912A>T: p.1304Cysext12). Conclusions The constellation of features in these AD and GD cases, including postnatal growth retardation of long bones and lung involvement, is reminiscent of the null ltbp3 mice phenotype. We conclude that LTBP3 is a novel component of the microfibrillar network involved in the acromelic dysplasia spectrum.
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ID Code: | 222066 | ||||||||||
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Item Type: | Contribution to Journal (Journal Article) | ||||||||||
Refereed: | Yes | ||||||||||
ORCID iD: |
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Measurements or Duration: | 8 pages | ||||||||||
Keywords: | acromelic dysplasia, acromicric dysplasia, fibrillins, geleophysic dysplasia, latent transforming factor-beta binding proteins (LTBP) | ||||||||||
DOI: | 10.1136/jmedgenet-2015-103647 | ||||||||||
ISSN: | 0022-2593 | ||||||||||
Pure ID: | 33071669 | ||||||||||
Divisions: | Past > QUT Faculties & Divisions > Faculty of Health Past > Institutes > Institute of Health and Biomedical Innovation |
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Copyright Owner: | Consult author(s) regarding copyright matters | ||||||||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||||||||
Deposited On: | 06 Nov 2021 15:40 | ||||||||||
Last Modified: | 31 Jul 2024 21:52 |
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