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

T Roscioli; EJ Kamsteeg; K Buysse; I Maystadt; J van Reeuwijk; C van den Elzen; E van Beusekom; M Riemersma; R Pfundt; LELM Vissers; M Schraders; U Altunoglu; MF Buckley; HG Brunner; B Grisart; HQ Zhou; JA Veltman; C (Christian) Gilissen; Grazia Verheijen - Mancini; P Delree; MA Willemsen; DP Ramadza; D Chitayat; C Bennett; E Sheridan; EAJ Peeters; GMB Tan-Sindhunata; CE de Die-Smulders; K DeVriendt; H Kayserili; OA El-Hashash; DL Stemple; DJ Lefeber; YY Lin; H van Bokhoven

doi:10.1038/ng.2253

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

T Roscioli, EJ Kamsteeg, K Buysse, I Maystadt, J van Reeuwijk, C van den Elzen, E van Beusekom, M Riemersma, R Pfundt, LELM Vissers, M Schraders, U Altunoglu, MF Buckley, HG Brunner, B Grisart, HQ Zhou, JA Veltman, C (Christian) Gilissen, Grazia Verheijen - Mancini, P DelreeMA Willemsen, DP Ramadza, D Chitayat, C Bennett, E Sheridan, EAJ Peeters, GMB Tan-Sindhunata, CE de Die-Smulders, K DeVriendt, H Kayserili, OA El-Hashash, DL Stemple, DJ Lefeber, YY Lin, H van Bokhoven

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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	Undefined/Unknown
Pages (from-to)	581-+
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2253
Publication status	Published - 2012

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EMC MGC-02-96-01

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10.1038/ng.2253

http://hdl.handle.net/1765/54326

Cite this

Roscioli, T., Kamsteeg, EJ., 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, HQ., Veltman, JA., Gilissen, C., Verheijen - Mancini, G., ... van Bokhoven, H. (2012). Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan. Nature Genetics, 44(5), 581-+. https://doi.org/10.1038/ng.2253

@article{01f87fb08eeb4a2580992dc8d131b893,

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 = "T Roscioli and EJ Kamsteeg and K Buysse and I Maystadt and {van Reeuwijk}, J and {van den Elzen}, C and {van Beusekom}, E and M Riemersma and R Pfundt and LELM Vissers and M Schraders and U Altunoglu and MF Buckley and HG Brunner and B Grisart and HQ Zhou and JA Veltman and Gilissen, {C (Christian)} and {Verheijen - Mancini}, Grazia and P Delree and MA Willemsen and DP Ramadza and D Chitayat and C Bennett and E Sheridan and EAJ Peeters and GMB Tan-Sindhunata and {de Die-Smulders}, CE and K DeVriendt and H Kayserili and OA El-Hashash and DL Stemple and DJ Lefeber and YY Lin and {van Bokhoven}, H",

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doi = "10.1038/ng.2253",

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Roscioli, T, Kamsteeg, EJ, 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, HQ, Veltman, JA, Gilissen, C, Verheijen - Mancini, G, 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, OA, Stemple, DL, Lefeber, DJ, Lin, YY & 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-+. 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, T

AU - Kamsteeg, EJ

AU - Buysse, K

AU - Maystadt, I

AU - van Reeuwijk, J

AU - van den Elzen, C

AU - van Beusekom, E

AU - Riemersma, M

AU - Pfundt, R

AU - Vissers, LELM

AU - Schraders, M

AU - Altunoglu, U

AU - Buckley, MF

AU - Brunner, HG

AU - Grisart, B

AU - Zhou, HQ

AU - Veltman, JA

AU - Gilissen, C (Christian)

AU - Verheijen - Mancini, Grazia

AU - Delree, P

AU - Willemsen, MA

AU - Ramadza, DP

AU - Chitayat, D

AU - Bennett, C

AU - Sheridan, E

AU - Peeters, EAJ

AU - Tan-Sindhunata, GMB

AU - de Die-Smulders, CE

AU - DeVriendt, K

AU - Kayserili, H

AU - El-Hashash, OA

AU - Stemple, DL

AU - Lefeber, DJ

AU - Lin, YY

AU - van Bokhoven, H

PY - 2012

Y1 - 2012

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.

U2 - 10.1038/ng.2253

DO - 10.1038/ng.2253

M3 - Article

C2 - 22522421

SN - 1061-4036

VL - 44

SP - 581-+

JO - Nature Genetics

JF - Nature Genetics

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ER -