Abstract
Stickler syndrome (SS) is a collagenopathy characterized by arthropathy and vitreoretinopathy with high myopia and cleft palate as common features. In a family with an autosomal recessive SS that does not map to genes known to cause autosomal recessive forms of SS, we combined autozygome and exome analysis to identify a novel missense variant in LOXL3 as the likely candidate cause. LOXL3 cross-links collagen II and its morphants phenocopy the craniofacial defects characteristic of collagen XI deficiency. We propose LOXL3 as a novel candidate gene for autosomal recessive SS.
This is a preview of subscription content, log in via an institution to check access.
References
Alkuraya FS (2013) The application of next-generation sequencing in the autozygosity mapping of human recessive diseases. Hum Genet 132:1197–1211
Evans AK, Rahbar R, Rogers GF, Mulliken JB, Volk MS (2006) Robin sequence: a retrospective review of 115 patients. Int J Pediatr Otorhinolaryngol 70:973–980
Lee J-E, Kim Y (2006) A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity. J Biol Chem 281:37282–37290
Lucero H, Kagan H (2006) Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell Mol Life Sci CMLS 63:2304–2316
Robin NH, Moran RT, Ala-Kokko L (2014) Stickler Syndrome. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews(r) [Internet], 1993–2015. University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1302/
van Boxtel AL, Gansner JM, Hakvoort HW, Snell H, Legler J, Gitlin JD (2011) Lysyl oxidase-like 3b is critical for cartilage maturation during zebrafish craniofacial development. Matrix Biol 30:178–187
Acknowledgments
We thank the family for their enthusiastic participation. We also thank the genotyping and sequencing core facilities at KFSHRC for their technical help. This study was supported in part by KACST 09-MED941-20 (FSA).
Conflict of interest
Authors declare no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
439_2015_1531_MOESM1_ESM.pdf
Figure S1. Cartoon of LOXL3 protein and alignment of its orthologs across species to show the high conservation of the mutated residue (PDF 86 kb)
Rights and permissions
About this article
Cite this article
Alzahrani, F., Al Hazzaa, S.A., Tayeb, H. et al. LOXL3, encoding lysyl oxidase-like 3, is mutated in a family with autosomal recessive Stickler syndrome. Hum Genet 134, 451–453 (2015). https://doi.org/10.1007/s00439-015-1531-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-015-1531-z