Neurologic syndrome associated with homozygous mutation at MAG sialic acid binding site.
The MAG gene encodes myelin-associated glycoprotein (MAG), an abundant protein involved in axon-glial interactions and myelination during nerve regeneration. Several members of a consanguineous family with a clinical syndrome reminiscent of Pelizaeus-Merzbacher disease and demyelinating leukodystrophy on brain MRI were recently found to harbor a homozygous missense p.Ser133Arg MAG mutation. Here, we report two brothers from a nonconsanguineous family afflicted with progressive cognitive impairment, neuropathy, ataxia, nystagmus, and gait disorder. Exome sequencing revealed the homozygous missense mutation p.Arg118His in MAG. This Arg118 residue in immunoglobulin domain 1 is critical for sialic acid binding, providing a compelling mechanistic basis for disease pathogenesis.
Department of Neurology Neuromuscular Medicine Johns Hopkins University School of Medicine Baltimore Maryland; Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland.
Ricardo H
RH
Roda
Laboratory of Sensorimotor Research National Eye Institute National Institutes of Health Bethesda Maryland.
Edmond J
EJ
FitzGibbon
Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland.
Houda
H
Boucekkine
Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland.
Alice B
AB
Schindler
Neurogenetics Branch National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland.
Craig
C
Blackstone