| Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome. | |
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MedLine Citation:
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PMID: 17436019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 alpha-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 alpha-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 alpha-dystroglycan protein. |
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Authors:
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Jeroen van Reeuwijk; Prabhjit K Grewal; Mustafa A M Salih; Daniel Beltrán-Valero de Bernabé; Jenny M McLaughlan; Caroline B Michielse; Ralf Herrmann; Jane E Hewitt; Alice Steinbrecher; Mohamed Z Seidahmed; Mohamed M Shaheed; Abdullah Abomelha; Han G Brunner; Hans van Bokhoven; Thomas Voit |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2007-04-14 |
Journal Detail:
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Title: Human genetics Volume: 121 ISSN: 0340-6717 ISO Abbreviation: Hum. Genet. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-13 Completed Date: 2007-09-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: Germany |
Other Details:
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Languages: eng Pagination: 685-90 Citation Subset: IM |
Affiliation:
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Department of Human Genetics 855, Radboud University Nijmegen Medical Center, Box 9101, 6500 HB Nijmegen, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Base Sequence Brain / abnormalities Consanguinity DNA Mutational Analysis Dystroglycans / chemistry, metabolism Exons Eye Abnormalities / genetics Female Gene Dosage Glycosylation Humans Infant Infant, Newborn Linkage (Genetics) Male Muscular Dystrophies / congenital*, genetics*, metabolism, pathology N-Acetylglucosaminyltransferases / genetics* Pedigree Phenotype Protein Processing, Post-Translational Sequence Deletion Syndrome |
| Grant Support | |
ID/Acronym/Agency:
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//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/DAG1 protein, human; 146888-27-9/Dystroglycans; EC 2.4.1.-/LARGE protein, human; EC 2.4.1.-/N-Acetylglucosaminyltransferases |
| Comments/Corrections | |
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