Tubulin beta 2B class IIb.
The TUBB2B gene provides instructions for making one version of a protein called beta-tubulin (β-tubulin). This protein is part of the tubulin family of proteins that form and organize cell structures called microtubules. Microtubules are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). They are composed of β-tubulin and a similar protein called alpha-tubulin (α-tubulin) that is produced from a different gene. Microtubules grow and shrink as tubulin proteins are added to and removed from the ends of fibers. This process allows cells to move and change shape.
β-tubulin produced from the TUBB2B gene is found primarily in the brain and in nerve cells (neurons). In neurons, microtubules are integral for the cells' movement to the proper location in the brain and for a process called axon guidance, by which specialized extensions of neurons (axons) reach their correct positions. Once in the right location, axons relay messages to and from the brain to control muscle movement and detect sensations such as touch, pain, heat, and sound.
At least one mutation in the TUBB2B gene has been found to cause a rare form of congenital fibrosis of the extraocular muscles (CFEOM) called CFEOM3 with polymicrogyria. Individuals with this condition are unable to move their eyes normally; they have difficulty looking up, and they have droopy eyelids (ptosis). In addition, affected individuals have a brain malformation called polymicrogyria, in which the surface of the brain develops too many folds, and the folds are unusually small. Individuals with this form of CFEOM3 typically have intellectual disability.
The TUBB2B gene mutation that causes CFEOM3 with polymicrogyria changes a single protein building block (amino acid) in the β-tubulin protein. It replaces the amino acid glutamate with the amino acid lysine at protein position 421 (written as Glu421Lys or E421K). Microtubules that contain the altered β-tubulin protein do not grow and shrink as they should, which prevents axons from reaching their proper location. Nerves in the head and face (cranial nerves) that control muscles that surround the eyes (extraocular muscles) are particularly affected. Abnormal development of cranial nerves impairs the function of extraocular muscles, leading to the characteristic features of CFEOM such as restricted eye movement and droopy eyelids. It is unclear how the CFEOM-related change in the TUBB2B gene results in polymicrogyria.
Mutations in the TUBB2B gene have been identified in people with brain abnormalities affecting the surface of the brain (the cortex), which are classified as malformations of cortical development. These individuals do not have problems with extraocular muscles (described above). The brain abnormalities typically lead to intellectual disability in affected individuals. Brain malformations commonly associated with TUBB2B gene mutations result from abnormal development of the cortex and can include polymicrogyria (described above); reduced folding (simplified gyration); an abnormally smooth surface (lissencephaly), sometimes with an abnormally small head size (microlissencephaly); slits or clefts in one or both halves of the brain (schizencephaly); or other cortical abnormalities. In some affected individuals, a region of the brain called the cerebellum is particularly affected (cerebellar dysplasia). It is thought that mutations in the TUBB2B gene disrupt the movement of neurons and axons to their correct locations, altering brain development and leading to brain malformations.
class IIb beta-tubulin
TUBULIN, BETA, CLASS IIB