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Neurologic syndrome associated with homozygous mutation at MAG sialic acid binding site.

ABSTRACT: 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.

SUBMITTER: Roda RH

PROVIDER: S-EPMC4999596 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Neurologic syndrome associated with homozygous mutation at MAG sialic acid binding site.

Roda Ricardo H RH FitzGibbon Edmond J EJ Boucekkine Houda H Schindler Alice B AB Blackstone Craig C

Annals of clinical and translational neurology 20160623 8

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 impairme ...[more]

PMID: 27606346

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Neurologic syndrome associated with homozygous mutation at MAG sialic acid binding site.

Publications

Neurologic syndrome associated with homozygous mutation at MAG sialic acid binding site.

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