title: Disorders of Microtubule Function in Neurons: Imaging Correlates.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: From the Department of Radiology and Biomedical Imaging (C.A.M., A.J.B.), University of California, San Francisco, San Francisco, California.
authors.forename: C A
authors.identifier: http://orcid.org/0000-0003-4556-8460
authors.initials: CA
authors.lastname: Mutch
authors.affiliation: 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.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-7350-5136
authors.initials: A
authors.lastname: Poduri
authors.affiliation: Department of Neurology (A.P., M.S., B.B., C.A.W.), Harvard Medical School, Boston, Massachusetts.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-7044-2953
authors.initials: M
authors.lastname: Sahin
authors.affiliation: 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.
authors.forename: B
authors.identifier: http://orcid.org/0000-0003-4358-8126
authors.initials: B
authors.lastname: Barry
authors.affiliation: 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.
authors.forename: C A
authors.identifier: http://orcid.org/0000-0002-0156-2238
authors.initials: CA
authors.lastname: Walsh
authors.affiliation: 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.
authors.forename: A J
authors.identifier: http://orcid.org/0000-0003-4291-7346
authors.initials: AJ
authors.lastname: Barkovich
mesh_terms: D000328:Adult; D001921:Brain / Q000002:abnormalities*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008870:Microtubules / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D014404:Tubulin / Q000235:genetics*
chemical_list: D014404:Tubulin