Abstract
Walker–Warburg syndrome (WWS) is a genetically heterogeneous form of congenital muscular dystrophy with significant brain and ocular involvement. In a multiplex consanguineous family with severe WWS phenotype, autozygome-guided sequencing of previously reported WWS genes was negative. Exome sequencing followed by autozygome filtration revealed a homozygous two-base pair insertion in B3GNT1 (NM_006876.2:c.821_822insTT), leading to premature truncation of the protein (p.Glu274Aspfs*94). Recently, two missense mutations in this gene have been reported as probably causal in a family with WWS. This report describes the first truncating mutation in B3GNT1 and confirms that this gene, which plays a role in αDG glycosylation, is a bona fide disease gene in WWS.
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Acknowledgments
We thank the family for its enthusiastic participation. We also thank the Genotyping and Sequencing Core Facilities at KFSHRC for their technical help. This study was supported in part by DHFMR Collaborative Research Grant (FSA).
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Shaheen, R., Faqeih, E., Ansari, S. et al. A truncating mutation in B3GNT1 causes severe Walker–Warburg syndrome. Neurogenetics 14, 243–245 (2013). https://doi.org/10.1007/s10048-013-0367-8
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DOI: https://doi.org/10.1007/s10048-013-0367-8