title: Phenotypic spectrum of the tubulin-related disorders and functional implications of disease-causing mutations.
abstract: A spectrum of neurological disorders characterized by abnormal neuronal migration, differentiation, and axon guidance and maintenance have recently been attributed to missense and splice-site mutations in the genes that encode α-tubulin and β-tubulin isotypes TUBA1A, TUBA8, TUBB2B, and TUBB3, all of which putatively coassemble into neuronal microtubules. The resulting nervous system malformations can include different types of cortical malformations, defects in commissural fiber tracts, and degeneration of motor and sensory axons. Many clinical phenotypes and brain malformations are shared among the various mutations regardless of structural location and/or isotype, while others segregate with distinct amino acids or functional domains within tubulin. Collectively, these disorders provide novel paradigms for understanding the biological functions of microtubules and their core components in normal health and disease.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins Medical School, 725 North Wolfe St., PCTB 804, Baltimore, MD 21205, United States.
authors.forename: Max A
authors.initials: MA
authors.lastname: Tischfield
authors.forename: Gustav Y
authors.initials: GY
authors.lastname: Cederquist
authors.forename: Mohan L
authors.initials: ML
authors.lastname: Gupta
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Engle
mesh_terms: D006801:Humans; D008870:Microtubules / Q000502:physiology; D020125:Mutation, Missense; D009422:Nervous System Diseases / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D022821:RNA Splice Sites; C533522:TUBA1A protein, human; C408046:TUBA8 protein, human; C498585:TUBB3 protein, human; D014404:Tubulin