TY - JOUR
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
N1 - Publisher Copyright:
© 2015 American Academy of Neurology.
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.
UR - http://www.scopus.com/inward/record.url?scp=84929901174&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000001615
DO - 10.1212/WNL.0000000000001615
M3 - Article
C2 - 25934851
AN - SCOPUS:84929901174
SN - 0028-3878
VL - 84
SP - 2177
EP - 2182
JO - Neurology
JF - Neurology
IS - 21
ER -