Abstract
Autosomal recessive cutis laxa is a genetically heterogeneous condition. Its molecular basis is largely unknown. Recently, a combined disorder of N- and O-linked glycosylation was described in children with congenital cutis laxa in association with severe central nervous system involvement, brain migration defects, seizures and hearing loss. We report on seven additional patients with similar clinical features in combination with congenital disorder of glycosylation type IIx. On the basis of phenotype in 10 patients, we define an autosomal recessive cutis laxa syndrome. The patients have a complex phenotype of neonatal cutis laxa, transient feeding intolerance, late closure of the fontanel, characteristic facial features including down-slanting palpebral fissures, short nose and small mouth, and developmental delay. There is a variable degree of the central nervous system involvement and variable systemic presentation. The biochemical analysis using transferrin isoelectric focusing gives false negative results in some of the youngest patients. Analysis of the apolipoprotein C-III isoelectric focusing, however, is diagnostic in all cases.
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Acknowledgements
This work was supported by grants from EUROGLYCANET contract number 512131 and NIH grants HL073703 and HL084922. We are thankful for the support of H van Bokhoven, M Janssen, A Vogt and L Berendsen regarding the linkage and sequence analysis.
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Morava, E., Lefeber, D., Urban, Z. et al. Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation. Eur J Hum Genet 16, 28–35 (2008). https://doi.org/10.1038/sj.ejhg.5201947
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DOI: https://doi.org/10.1038/sj.ejhg.5201947
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