POU domain, class 3, transcription factor 4 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''POU3F4''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
found on the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...
.
POU3F4 is involved in the patterning of the
neural tube
In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, ...
and both the
paraventricular and
supraoptic nuclei of the
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...
in the developing embryo. During development, POU3F4 is also expressed in the
mesenchyme
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...
of the
periotic bone surrounding the
inner ear
The inner ear (internal ear, auris interna) is the innermost part of the vertebrate ear. In vertebrates, the inner ear is mainly responsible for sound detection and balance. In mammals, it consists of the bony labyrinth, a hollow cavity in th ...
. A
“knockout” mice model displayed that alteration to the POU3F4 gene interrupted this mesenchymal cell differentiation in the superior
semicircular canal
In mathematics (and more specifically geometry), a semicircle is a one-dimensional locus of points that forms half of a circle. The full arc of a semicircle always measures 180° (equivalently, radians, or a half-turn). It has only one line o ...
. The deformities observed in mice were similar to those in humans with X-linked non-syndromic deafness (DFN-3).
Clinical significance
Genetic testing
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
on various persons has confirmed that mutations of the POU3F4 gene cause X-linked
non-syndromic deafness
Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Genetic changes are related to the follow ...
(DFN-3).
These known mutations include:
* Missense mutation causing the substitution of amino acid
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
for
glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
at position 216
* A deletion of the POU3F4 gene and 530 more kilobases upstream
* An amino acid substitution of serine for
leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- ...
(S228L) in POU3F4
* Frameshift truncation and extension mutations at the POU3F4 C-terminus
Physical anomalies caused by POU3F4 mutations that have been recognized by
high resolution computed tomography (HRCT) and
magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI) include absence of the central axis of the
cochlea
The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory o ...
, an abnormally wide lateral internal
auditory canal
The ear canal (external acoustic meatus, external auditory meatus, EAM) is a pathway running from the outer ear to the middle ear. The adult human ear canal extends from the pinna to the eardrum and is about in length and in diameter.
Stru ...
and a thickened stapes footplate. These anomalies are associated with X-linked
non-syndromic deafness.
References
Further reading
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External links
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POU-domain proteins
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