Absence of α-and β-dystroglycan is associated with Walker-Warburg syndrome

Moniek Riemersma; Hanna Mandel; Ellen Van Beusekom; Isabella Gazzoli; Tony Roscioli; Ayelet Eran; Ruth Gershoni-Baruch; Moran Gershoni; Shmuel Pietrokovski; Lisenka E. Vissers; Dirk J. Lefeber; Michèl A. Willemsen; Ron A. Wevers; Hans Van Bokhoven

doi:10.1212/WNL.0000000000001615

Absence of α-and β-dystroglycan is associated with Walker-Warburg syndrome

Moniek Riemersma, Hanna Mandel, Ellen Van Beusekom, Isabella Gazzoli, Tony Roscioli, Ayelet Eran, Ruth Gershoni-Baruch, Moran Gershoni, Shmuel Pietrokovski, Lisenka E. Vissers, Dirk J. Lefeber, Michèl A. Willemsen, Ron A. Wevers, Hans Van Bokhoven^*

^*Corresponding author for this work

Department of Molecular Genetics

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

33 Citations (Scopus)

Abstract

Objective: To identify the underlying genetic defect in 5 patients from a consanguineous family with a Walker-Warburg phenotype, together with intracranial calcifications. Methods: Homozygosity mapping and exome sequencing, followed by Sanger sequencing of the obtained candidate gene, was performed. Expression of the candidate gene was tested by reverse transcription PCR. Patient fibroblasts were converted to myotubes, and the expression and function of dystroglycan was tested by Western blotting. Results: We detected a homozygous loss-of-function frameshift mutation in the DAG1 gene and showed that this mutation results in a complete absence of both α-and β-dystroglycan. Conclusions: A loss-of-function mutation in DAG1 can result in Walker-Warburg syndrome and is not embryonic lethal.

Original language	English
Pages (from-to)	2177-2182
Number of pages	6
Journal	Neurology
Volume	84
Issue number	21
DOIs	https://doi.org/10.1212/WNL.0000000000001615
Publication status	Published - 26 May 2015

All Science Journal Classification (ASJC) codes

Clinical Neurology

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Riemersma, M., Mandel, H., Van Beusekom, E., Gazzoli, I., Roscioli, T., Eran, A., Gershoni-Baruch, R., Gershoni, M., Pietrokovski, S., Vissers, L. E., Lefeber, D. J., Willemsen, M. A., Wevers, R. A., & Van Bokhoven, H. (2015). Absence of α-and β-dystroglycan is associated with Walker-Warburg syndrome. Neurology, 84(21), 2177-2182. https://doi.org/10.1212/WNL.0000000000001615

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abstract = "Objective: To identify the underlying genetic defect in 5 patients from a consanguineous family with a Walker-Warburg phenotype, together with intracranial calcifications. Methods: Homozygosity mapping and exome sequencing, followed by Sanger sequencing of the obtained candidate gene, was performed. Expression of the candidate gene was tested by reverse transcription PCR. Patient fibroblasts were converted to myotubes, and the expression and function of dystroglycan was tested by Western blotting. Results: We detected a homozygous loss-of-function frameshift mutation in the DAG1 gene and showed that this mutation results in a complete absence of both α-and β-dystroglycan. Conclusions: A loss-of-function mutation in DAG1 can result in Walker-Warburg syndrome and is not embryonic lethal.",

author = "Moniek Riemersma and Hanna Mandel and {Van Beusekom}, Ellen and Isabella Gazzoli and Tony Roscioli and Ayelet Eran and Ruth Gershoni-Baruch and Moran Gershoni and Shmuel Pietrokovski and Vissers, {Lisenka E.} and Lefeber, {Dirk J.} and Willemsen, {Mich{\`e}l A.} and Wevers, {Ron A.} and {Van Bokhoven}, Hans",

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doi = "10.1212/WNL.0000000000001615",

language = "English",

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T1 - Absence of α-and β-dystroglycan is associated with Walker-Warburg syndrome

AU - Riemersma, Moniek

AU - Mandel, Hanna

AU - Van Beusekom, Ellen

AU - Gazzoli, Isabella

AU - Roscioli, Tony

AU - Eran, Ayelet

AU - Gershoni-Baruch, Ruth

AU - Gershoni, Moran

AU - Pietrokovski, Shmuel

AU - Vissers, Lisenka E.

AU - Lefeber, Dirk J.

AU - Willemsen, Michèl A.

AU - Wevers, Ron A.

AU - Van Bokhoven, Hans

PY - 2015/5/26

Y1 - 2015/5/26

N2 - Objective: To identify the underlying genetic defect in 5 patients from a consanguineous family with a Walker-Warburg phenotype, together with intracranial calcifications. Methods: Homozygosity mapping and exome sequencing, followed by Sanger sequencing of the obtained candidate gene, was performed. Expression of the candidate gene was tested by reverse transcription PCR. Patient fibroblasts were converted to myotubes, and the expression and function of dystroglycan was tested by Western blotting. Results: We detected a homozygous loss-of-function frameshift mutation in the DAG1 gene and showed that this mutation results in a complete absence of both α-and β-dystroglycan. Conclusions: A loss-of-function mutation in DAG1 can result in Walker-Warburg syndrome and is not embryonic lethal.

AB - Objective: To identify the underlying genetic defect in 5 patients from a consanguineous family with a Walker-Warburg phenotype, together with intracranial calcifications. Methods: Homozygosity mapping and exome sequencing, followed by Sanger sequencing of the obtained candidate gene, was performed. Expression of the candidate gene was tested by reverse transcription PCR. Patient fibroblasts were converted to myotubes, and the expression and function of dystroglycan was tested by Western blotting. Results: We detected a homozygous loss-of-function frameshift mutation in the DAG1 gene and showed that this mutation results in a complete absence of both α-and β-dystroglycan. Conclusions: A loss-of-function mutation in DAG1 can result in Walker-Warburg syndrome and is not embryonic lethal.

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DO - 10.1212/WNL.0000000000001615

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VL - 84

SP - 2177

EP - 2182

JO - Neurology

JF - Neurology

IS - 21

ER -

Absence of α-and β-dystroglycan is associated with Walker-Warburg syndrome

Abstract

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