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

Ricardo H. Roda; Edmond J. FitzGibbon; Houda Boucekkine; Alice B. Schindler; Craig Blackstone

doi:10.1002/acn3.329

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

Ricardo H. Roda, Edmond J. FitzGibbon, Houda Boucekkine, Alice B. Schindler, Craig Blackstone

School of Medicine

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Pages (from-to)	650-654
Number of pages	5
Journal	Annals of Clinical and Translational Neurology
Volume	3
Issue number	8
DOIs	https://doi.org/10.1002/acn3.329
State	Published - Aug 1 2016

ASJC Scopus subject areas

General Neuroscience
Clinical Neurology

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title = "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.",

author = "Roda, {Ricardo H.} and FitzGibbon, {Edmond J.} and Houda Boucekkine and Schindler, {Alice B.} and Craig Blackstone",

note = "Funding Information: We thank Elizabeth Hartnett for help with patient scheduling and the Johns Hopkins Hospital Cutaneous Nerve Laboratory for performing the biopsy analysis. We also thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison; a list of contributing groups is available at http://exac.broadinstitute.org/about. Publisher Copyright: Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association",

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AU - Roda, Ricardo H.

AU - FitzGibbon, Edmond J.

AU - Boucekkine, Houda

AU - Schindler, Alice B.

AU - Blackstone, Craig

N1 - Funding Information: We thank Elizabeth Hartnett for help with patient scheduling and the Johns Hopkins Hospital Cutaneous Nerve Laboratory for performing the biopsy analysis. We also thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison; a list of contributing groups is available at http://exac.broadinstitute.org/about. Publisher Copyright: Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association

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N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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