Abstract
ALG6-CDG (formerly named CDG-Ic) (phenotype OMIM 603147, genotype OMIM 604566), is caused by defective endoplasmic reticulum α-1,3-glucosyltransferase (E.C 2.4.1.267) in the N-glycan assembly pathway (Grünewald et al. 2000). It is the second most frequent N-glycosylation disorder after PMM2-CDG; some 37 patients have been reported with 21 different ALG6 gene mutations (Haeuptle & Hennet 2009; Al-Owain 2010). We report on the clinical and biochemical findings of five novel Caucasian South African patients. The first patient had a severe neuro-gastrointestinal presentation. He was compound heterozygous for the known c.998C>T (p.A333V) mutation and the novel c.1338dupA (p.V447SfsX44) mutation. Four more patients, presenting with classical neurological involvement were identified and were compound heterozygous for the known c.257 + 5G>A splice mutation and the c.680G>A (p.G227E) missense mutation. The patients belong to a semi-isolated Caucasian community that may have originated from European pioneers who colonized South Africa in the seventeenth/eighteenth centuries.
Competing interests: none declared
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Acknowledgments
We thank the Laboratory for Inherited Metabolic Defects in South Africa (Potchefstroom) (http:///www.pliem.co.za) for the initial transferrin IEF analyses and for gathering of diagnostic material from South African CDG patients (a special thanks to Ansie Mienie, Elmarie Davoren, and Amaria van Huysteen). We appreciate sample referral from the Newborn Screening lab in South Africa (http://www.newbornscreening.co.za). We also want to express our gratitude to the colleagues of the Laboratory Genetic Metabolic diseases at the Academic Medical Centre, University of Amsterdam, who confirmed the South African CDG patients with serum transferrin IEF analyses. We thank Liesbeth Keldermans and Sandra Van Aerschot from the Department of Human Genetics and the Centre for Metabolic Diseases, at the University of Leuven, for excellent technical assistance. We are grateful to the patients and their families as well as to the referral doctors for their participation and support in this study.
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Communicated by: Eva Morava, MD PhD
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Dercksen, M. et al. (2012). ALG6-CDG in South Africa: Genotype-Phenotype Description of Five Novel Patients. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, 2012/5. JIMD Reports, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_150
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DOI: https://doi.org/10.1007/8904_2012_150
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