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AJNR Am J Neuroradiol. 2016 Mar;37(3):528-35. doi: 10.3174/ajnr.A4552. Epub 2015 Nov 12.

Disorders of Microtubule Function in Neurons: Imaging Correlates.

Author information

1
From the Department of Radiology and Biomedical Imaging (C.A.M., A.J.B.), University of California, San Francisco, San Francisco, California.
2
Epilepsy Genetics Program (A.P., B.B., C.A.W.), Division of Epilepsy and Clinical Neurophysiology F.M. Kirby Neurobiology Center (A.P., B.B., C.A.W.) Division of Genetics and Genomics (B.B., C.A.W.), Department of Medicine, Manton Center for Orphan Disease Research and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts Department of Neurology (A.P., M.S., B.B., C.A.W.), Harvard Medical School, Boston, Massachusetts.
3
Department of Neurology (A.P., M.S., B.B., C.A.W.), Harvard Medical School, Boston, Massachusetts.
4
Epilepsy Genetics Program (A.P., B.B., C.A.W.), Division of Epilepsy and Clinical Neurophysiology F.M. Kirby Neurobiology Center (A.P., B.B., C.A.W.) Department of Neurology (A.P., M.S., B.B., C.A.W.), Harvard Medical School, Boston, Massachusetts.
5
From the Department of Radiology and Biomedical Imaging (C.A.M., A.J.B.), University of California, San Francisco, San Francisco, California James.Barkovich@ucsf.edu.

Abstract

BACKGROUND AND PURPOSE:

A number of recent studies have described malformations of cortical development with mutations of components of microtubules and microtubule-associated proteins. Despite examinations of a large number of MRIs, good phenotype-genotype correlations have been elusive. Additionally, most of these studies focused exclusively on cerebral cortical findings. The purpose of this study was to characterize imaging findings associated with disorders of microtubule function.

MATERIALS AND METHODS:

MRIs from 18 patients with confirmed tubulin mutations (8 TUBA1A, 5 TUBB2B, and 5 TUBB3) and 15 patients with known mutations of the genes encoding microtubule-associated proteins (5 LIS1, 4 DCX, and 6 DYNC1H1) were carefully visually analyzed and compared. Specific note was made of the cortical gyral pattern, basal ganglia, and white matter to assess internal capsular size, cortical thickness, ventricular and cisternal size, and the size and contours of the brain stem, cerebellar hemispheres and vermis, and the corpus callosum of patients with tubulin and microtubule-associated protein gene mutations. Results were determined by unanimous consensus of the authors.

RESULTS:

All patients had abnormal findings on MR imaging. A large number of patients with tubulin gene mutations were found to have multiple cortical and subcortical abnormalities, including microcephaly, ventriculomegaly, abnormal gyral and sulcal patterns (termed "dysgyria"), a small or absent corpus callosum, and a small pons. All patients with microtubule-associated protein mutations also had abnormal cerebral cortices (predominantly pachygyria and agyria), but fewer subcortical abnormalities were noted.

CONCLUSIONS:

Comparison of MRIs from patients with known mutations of tubulin genes and microtubule-associated proteins allows the establishment of some early correlations of phenotype with genotype and may assist in identification and diagnosis of these rare disorders.

PMID:
26564436
PMCID:
PMC4792764
DOI:
10.3174/ajnr.A4552
[Indexed for MEDLINE]
Free PMC Article

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