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- Title
Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome.
- Authors
van Reeuwijk, Jeroen; Grewal, Prabhjit K.; Salih, Mustafa A. M.; de Bernabé, Daniel Beltrán-Valero; McLaughlan, Jenny M.; Michielse, Caroline B.; Herrmann, Ralf; Ewitt, Jane E.; Steinbrecher, Alice; Seidahmed, Mohamed Z.; Shaheed, Mohamed M.; Abomelha, Abdullah; Brunner, Han G.; van Bokhoven, Hans; Voit, Thomas
- Abstract
Intragenic homozygous deletions in the Large gene are associated with a severe neuromuscular phenotype in the myodystrophy ( myd) mouse. These mutations result in a virtual lack of glycosylation of α-dystroglycan. Compound heterozygous LARGE mutations have been reported in a single human patient, manifesting with mild congenital muscular dystrophy (CMD) and severe mental retardation. These mutations are likely to retain some residual LARGE glycosyltransferase activity as indicated by residual α-dystroglycan glycosylation in patient cells. We hypothesized that more severe LARGE mutations are associated with a more severe CMD phenotype in humans. Here we report a 63-kb intragenic LARGE deletion in a family with Walker-Warburg syndrome (WWS), which is characterized by CMD, and severe structural brain and eye malformations. This finding demonstrates that LARGE gene mutations can give rise to a wide clinical spectrum, similar as for other genes that have a role in the post-translational modification of the α-dystroglycan protein.
- Subjects
GENOTYPE-environment interaction; PHENOTYPES; GENETIC regulation; GLYCOSYLTRANSFERASE genes; GLYCOSYLATION; GENETIC mutation
- Publication
Human Genetics, 2007, Vol 121, Issue 6, p685
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-007-0362-y