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

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 languageEnglish
Pages (from-to)2177-2182
Number of pages6
JournalNeurology
Volume84
Issue number21
DOIs
StatePublished - 26 May 2015
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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