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Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome
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, man...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914248/ https://www.ncbi.nlm.nih.gov/pubmed/17436019 http://dx.doi.org/10.1007/s00439-007-0362-y |
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author | van Reeuwijk, Jeroen Grewal, Prabhjit K. Salih, Mustafa A. M. Beltrán-Valero de Bernabé, Daniel McLaughlan, Jenny M. Michielse, Caroline B. Herrmann, Ralf Hewitt, Jane E. Steinbrecher, Alice Seidahmed, Mohamed Z. Shaheed, Mohamed M. Abomelha, Abdullah Brunner, Han G. van Bokhoven, Hans Voit, Thomas |
author_facet | van Reeuwijk, Jeroen Grewal, Prabhjit K. Salih, Mustafa A. M. Beltrán-Valero de Bernabé, Daniel McLaughlan, Jenny M. Michielse, Caroline B. Herrmann, Ralf Hewitt, Jane E. Steinbrecher, Alice Seidahmed, Mohamed Z. Shaheed, Mohamed M. Abomelha, Abdullah Brunner, Han G. van Bokhoven, Hans Voit, Thomas |
author_sort | van Reeuwijk, Jeroen |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-007-0362-y) contains supplementary material, which is available to authorized users. |
format | Text |
id | pubmed-1914248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-19142482007-07-12 Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome van Reeuwijk, Jeroen Grewal, Prabhjit K. Salih, Mustafa A. M. Beltrán-Valero de Bernabé, Daniel McLaughlan, Jenny M. Michielse, Caroline B. Herrmann, Ralf Hewitt, Jane E. Steinbrecher, Alice Seidahmed, Mohamed Z. Shaheed, Mohamed M. Abomelha, Abdullah Brunner, Han G. van Bokhoven, Hans Voit, Thomas Hum Genet Original Investigation 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-007-0362-y) contains supplementary material, which is available to authorized users. Springer-Verlag 2007-04-14 2007-07 /pmc/articles/PMC1914248/ /pubmed/17436019 http://dx.doi.org/10.1007/s00439-007-0362-y Text en © Springer-Verlag 2007 |
spellingShingle | Original Investigation van Reeuwijk, Jeroen Grewal, Prabhjit K. Salih, Mustafa A. M. Beltrán-Valero de Bernabé, Daniel McLaughlan, Jenny M. Michielse, Caroline B. Herrmann, Ralf Hewitt, Jane E. Steinbrecher, Alice Seidahmed, Mohamed Z. Shaheed, Mohamed M. Abomelha, Abdullah Brunner, Han G. van Bokhoven, Hans Voit, Thomas Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome |
title | Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome |
title_full | Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome |
title_fullStr | Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome |
title_full_unstemmed | Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome |
title_short | Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome |
title_sort | intragenic deletion in the large gene causes walker-warburg syndrome |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914248/ https://www.ncbi.nlm.nih.gov/pubmed/17436019 http://dx.doi.org/10.1007/s00439-007-0362-y |
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