Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan

Tony Roscioli; Erik-Jan Kamsteeg; Karen Buysse; Isabelle Maystadt; Jeroen van Reeuwijk; Christa van den Elzen; Ellen van Beusekom; Moniek Riemersma; Rolph Pfundt; Lisenka E. L. M. Vissers; Margit Schraders; Umut Altunoglu; Michael F. Buckley; Han G. Brunner; Bernard Grisart; Huiqing Zhou; Joris A. Veltman; Christian Gilissen; Grazia M. S. Mancini; Paul Delree; Michel A. Willemsen; Danijela Petkovic Ramadza; David Chitayat; Christopher Bennett; Eamonn Sheridan; Els A. J. Peeters; Gita M. B. Tan-Sindhunata; Christine E. de Die-Smulders; Koenraad Devriendt; Hulya Kayserili; Osama Abd El-Fattah El-Hashash; Derek L. Stemple; Dirk J. Lefeber; Yung-Yao Lin; Hans van Bokhoven

doi:10.1038/ng.2253

Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan

Tony Roscioli, Erik-Jan Kamsteeg, Karen Buysse, Isabelle Maystadt, Jeroen van Reeuwijk, Christa van den Elzen, Ellen van Beusekom, Moniek Riemersma, Rolph Pfundt, Lisenka E. L. M. Vissers, Margit Schraders, Umut Altunoglu, Michael F. Buckley, Han G. Brunner, Bernard Grisart, Huiqing Zhou, Joris A. Veltman, Christian Gilissen, Grazia M. S. Mancini, Paul DelreeMichel A. Willemsen, Danijela Petkovic Ramadza, David Chitayat, Christopher Bennett, Eamonn Sheridan, Els A. J. Peeters, Gita M. B. Tan-Sindhunata, Christine E. de Die-Smulders, Koenraad Devriendt, Hulya Kayserili, Osama Abd El-Fattah El-Hashash, Derek L. Stemple, Dirk J. Lefeber, Yung-Yao Lin^*, Hans van Bokhoven

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant alpha-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated alpha-dystroglycan. These results implicate ISPD in alpha-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.

Original language	English
Pages (from-to)	581–585
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2253
Publication status	Published - May 2012

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Roscioli, T., Kamsteeg, E.-J., Buysse, K., Maystadt, I., van Reeuwijk, J., van den Elzen, C., van Beusekom, E., Riemersma, M., Pfundt, R., Vissers, L. E. L. M., Schraders, M., Altunoglu, U., Buckley, M. F., Brunner, H. G., Grisart, B., Zhou, H., Veltman, J. A., Gilissen, C., Mancini, G. M. S., ... van Bokhoven, H. (2012). Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan. Nature Genetics, 44(5), 581–585. https://doi.org/10.1038/ng.2253

@article{2143af937aa043049522d2e2c892194c,

title = "Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan",

abstract = "Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant alpha-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated alpha-dystroglycan. These results implicate ISPD in alpha-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.",

author = "Tony Roscioli and Erik-Jan Kamsteeg and Karen Buysse and Isabelle Maystadt and {van Reeuwijk}, Jeroen and {van den Elzen}, Christa and {van Beusekom}, Ellen and Moniek Riemersma and Rolph Pfundt and Vissers, {Lisenka E. L. M.} and Margit Schraders and Umut Altunoglu and Buckley, {Michael F.} and Brunner, {Han G.} and Bernard Grisart and Huiqing Zhou and Veltman, {Joris A.} and Christian Gilissen and Mancini, {Grazia M. S.} and Paul Delree and Willemsen, {Michel A.} and Ramadza, {Danijela Petkovic} and David Chitayat and Christopher Bennett and Eamonn Sheridan and Peeters, {Els A. J.} and Tan-Sindhunata, {Gita M. B.} and {de Die-Smulders}, {Christine E.} and Koenraad Devriendt and Hulya Kayserili and El-Hashash, {Osama Abd El-Fattah} and Stemple, {Derek L.} and Lefeber, {Dirk J.} and Yung-Yao Lin and {van Bokhoven}, Hans",

year = "2012",

month = may,

doi = "10.1038/ng.2253",

language = "English",

volume = "44",

pages = "581–585",

journal = "Nature Genetics",

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Roscioli, T, Kamsteeg, E-J, Buysse, K, Maystadt, I, van Reeuwijk, J, van den Elzen, C, van Beusekom, E, Riemersma, M, Pfundt, R, Vissers, LELM, Schraders, M, Altunoglu, U, Buckley, MF, Brunner, HG, Grisart, B, Zhou, H, Veltman, JA, Gilissen, C, Mancini, GMS, Delree, P, Willemsen, MA, Ramadza, DP, Chitayat, D, Bennett, C, Sheridan, E, Peeters, EAJ, Tan-Sindhunata, GMB, de Die-Smulders, CE, Devriendt, K, Kayserili, H, El-Hashash, OAE-F, Stemple, DL, Lefeber, DJ, Lin, Y-Y & van Bokhoven, H 2012, 'Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan', Nature Genetics, vol. 44, no. 5, pp. 581–585. https://doi.org/10.1038/ng.2253

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T1 - Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan

AU - Roscioli, Tony

AU - Kamsteeg, Erik-Jan

AU - Buysse, Karen

AU - Maystadt, Isabelle

AU - van Reeuwijk, Jeroen

AU - van den Elzen, Christa

AU - van Beusekom, Ellen

AU - Riemersma, Moniek

AU - Pfundt, Rolph

AU - Vissers, Lisenka E. L. M.

AU - Schraders, Margit

AU - Altunoglu, Umut

AU - Buckley, Michael F.

AU - Brunner, Han G.

AU - Grisart, Bernard

AU - Zhou, Huiqing

AU - Veltman, Joris A.

AU - Gilissen, Christian

AU - Mancini, Grazia M. S.

AU - Delree, Paul

AU - Willemsen, Michel A.

AU - Ramadza, Danijela Petkovic

AU - Chitayat, David

AU - Bennett, Christopher

AU - Sheridan, Eamonn

AU - Peeters, Els A. J.

AU - Tan-Sindhunata, Gita M. B.

AU - de Die-Smulders, Christine E.

AU - Devriendt, Koenraad

AU - Kayserili, Hulya

AU - El-Hashash, Osama Abd El-Fattah

AU - Stemple, Derek L.

AU - Lefeber, Dirk J.

AU - Lin, Yung-Yao

AU - van Bokhoven, Hans

PY - 2012/5

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N2 - Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant alpha-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated alpha-dystroglycan. These results implicate ISPD in alpha-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.

AB - Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant alpha-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated alpha-dystroglycan. These results implicate ISPD in alpha-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.

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DO - 10.1038/ng.2253

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