POU domain, class 3, transcription factor 4 is a
protein that in humans is encoded by the POU3F4gene found on the
X chromosome.[5][6][7]
POU3F4 is involved in the patterning of the
neural tube and both the
paraventricular and
supraoptic nuclei of the
hypothalamus in the developing embryo.[8] During development, POU3F4 is also expressed in the
mesenchyme of the
periotic bone surrounding the
inner ear.[9] A
“knockout” mice model displayed that alteration to the POU3F4 gene interrupted this mesenchymal cell differentiation in the superior
semicircular canal. The deformities observed in mice were similar to those in humans with X-linked non-syndromic deafness (DFN-3).[10]
Clinical significance
Genetic testing on various persons has confirmed that mutations of the POU3F4 gene cause X-linked
non-syndromic deafness (DFN-3).[11] These known mutations include:
Missense mutation causing the substitution of amino acid
glycine for
glutamic acid at position 216[12]
A deletion of the POU3F4 gene and 530 more kilobases upstream[13]
An amino acid substitution of serine for
leucine (S228L) in POU3F4[13]
Frameshift truncation and extension mutations at the POU3F4 C-terminus[14]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Douville PJ, Atanasoski S, Tobler A, Fontana A, Schwab ME (Mar 1994). "The brain-specific POU-box gene Brn4 is a sex-linked transcription factor located on the human and mouse X chromosomes". Mammalian Genome. 5 (3): 180–2.
doi:
10.1007/BF00352353.
PMID7911044.
S2CID22846323.
^Bitner-Glindzicz M, Turnpenny P, Höglund P, Kääriäinen H, Sankila EM, van der Maarel SM, de Kok YJ, Ropers HH, Cremers FP, Pembrey M (Aug 1995). "Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3". Human Molecular Genetics. 4 (8): 1467–9.
doi:
10.1093/hmg/4.8.1467.
hdl:2066/22078.
PMID7581392.
^Sobol SE, Teng X, Crenshaw E, III. Abnormal Mesenchymal Differentiation in the Superior Semicircular Canal of Brn4/Pou3f4 Knockout Mice. Arch Otolaryngol Head Neck Surg. 2005;131(1):41-45.
^Li J, Cheng J, Lu Y, Lu Y, Chen A, Sun Y, Kang D, Zhang X, Dai P, Han D, Yuan H (Dec 2010). "Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese family with X-linked nonsyndromic hearing loss". Journal of Genetics and Genomics = Yi Chuan Xue Bao. 37 (12): 787–93.
doi:
10.1016/S1673-8527(09)60096-5.
PMID21193157.
^Gong WX, Gong RZ, Zhao B (Oct 2014). "HRCT and MRI findings in X-linked non-syndromic deafness patients with a POU3F4 mutation". International Journal of Pediatric Otorhinolaryngology. 78 (10): 1756–62.
doi:
10.1016/j.ijporl.2014.08.013.
PMID25175280.
Hagiwara H, Tamagawa Y, Kitamura K, Kodera K (Oct 1998). "A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3)". The Laryngoscope. 108 (10): 1544–7.
doi:
10.1097/00005537-199810000-00022.
PMID9778298.
S2CID44565001.
Xia AP, Kikuchi T, Minowa O, Katori Y, Oshima T, Noda T, Ikeda K (Apr 2002). "Late-onset hearing loss in a mouse model of DFN3 non-syndromic deafness: morphologic and immunohistochemical analyses". Hearing Research. 166 (1–2): 150–8.
doi:
10.1016/S0378-5955(02)00309-X.
PMID12062767.
S2CID41535704.