, Volume 14, Issue 3–4, pp 205–213 | Cite as

Homozygous dystroglycan mutation associated with a novel muscle–eye–brain disease-like phenotype with multicystic leucodystrophy

  • Tobias Geis
  • Klaus Marquard
  • Tanja Rödl
  • Christof Reihle
  • Sophie Schirmer
  • Thekla von Kalle
  • Antje Bornemann
  • Ute Hehr
  • Markus Blankenburg
Original Article


Defects in dystroglycan post-translational modification result in congenital muscular dystrophy with or without additional eye and brain involvement, are referred to as secondary dystroglycanopathies and have been associated with mutations in 11 different genes encoding glycosyltransferases or associated proteins. However, only one patient with a mutation in the dystroglycan encoding gene DAG1 itself has been described before. We here report a homozygous novel DAG1 missense mutation c.2006G>T predicted to result in the amino acid substitution p.Cys669Phe in the β-subunit of dystroglycan in two Libyan siblings. The affected girls presented with a severe muscle–eye–brain disease-like phenotype with distinct additional findings of macrocephaly and extended bilateral multicystic white matter disease, overlapping with the cerebral findings in patients with megalencephalic leucoencephalopathy with subcortical cysts. This novel clinical phenotype observed in our patients further expands the clinical spectrum of dystroglycanopathies and suggests a role of DAG1 not only for dystroglycanopathies but also for some forms of more extensive and multicystic leucodystrophy.


Dystroglycan DAG1 Muscle–eye–brain disease (MEB) Multicystic leucodystrophy Cystic white matter disease Megalencephalic leucoencephalopathy with subcortical cysts (MLC) 



The authors wish to thank the family for their participation in this study and M. Becher and F. Müller for excellent technical assistance. The authors declare that the study complies with the laws of the country in which it was performed.

Conflict of interest

The authors declare that they do not have a conflict of interest.

Electronic supplementary material

Supplementary material

10048_2013_374_MOESM1_ESM.ppt (100 kb)
ESM 1 (PPT 100 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Tobias Geis
    • 1
  • Klaus Marquard
    • 2
  • Tanja Rödl
    • 3
  • Christof Reihle
    • 2
  • Sophie Schirmer
    • 3
  • Thekla von Kalle
    • 4
  • Antje Bornemann
    • 5
  • Ute Hehr
    • 3
    • 6
  • Markus Blankenburg
    • 2
  1. 1.Department of Pediatric Neurology, Klinik St. HedwigUniversity Children’s Hospital Regensburg (KUNO)RegensburgGermany
  2. 2.Department of Pediatric NeurologyKlinikum Stuttgart, OlgahospitalStuttgartGermany
  3. 3.Center for Human GeneticsRegensburgGermany
  4. 4.Department of Pediatric RadiologyKlinikum Stuttgart, OlgahospitalStuttgartGermany
  5. 5.Department of NeuropathologyUniversity of TübingenTübingenGermany
  6. 6.Department of Human GeneticsUniversity of RegensburgRegensburgGermany

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