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POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4gene found on the X chromosome.[1][2][3]
POU3F4 is involved in the patterning of the neural tube and both the paraventricular and supraoptic nuclei of the hypothalamus in the developing embryo.[4] During development, POU3F4 is also expressed in the mesenchyme of the periotic bone surrounding the inner ear.[5] 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).[6]
Genetic testing on various persons has confirmed that mutations of the POU3F4 gene cause X-linked non-syndromic deafness (DFN-3).[7] These known mutations include:
Missense mutation causing the substitution of amino acid glycine for glutamic acid at position 216[8]
A deletion of the POU3F4 gene and 530 more kilobases upstream[9]
An amino acid substitution of serine for leucine (S228L) in POU3F4[9]
Frameshift truncation and extension mutations at the POU3F4 C-terminus[10]
Physical anomalies caused by POU3F4 mutations that have been recognized by high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) include absence of the central axis of the cochlea, an abnormally wide lateral internal auditory canal and a thickened stapes footplate. These anomalies are associated with X-linked non-syndromic deafness.[11]
References
↑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.
↑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.
↑Mathis JM, Simmons DM, He X, Swanson LW, Rosenfeld MG (1992). "Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression". The EMBO Journal. 11 (7): 2551–2561.
↑Phippard D, Heydemann A, Lechner M, Lu L, Lee D, Kyin T, Crenshaw EB (1998). "3rd Changes in the subcellular localization of the Brn4 gene product precede mesenchymal remodeling of the otic capsule". Hear. Res. 120 (1–2): 77–85. doi:10.1016/s0378-5955(98)00059-8. PMID9667433.
↑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.
↑de Kok YJ, van der Maarel SM, Bitner-Glindzicz M, Huber I, Monaco AP, Malcolm S, Pembrey ME, Ropers HH, Cremers FP (Feb 1995). "Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4". Science. 267 (5198): 685–8. doi:10.1126/science.7839145. hdl:2066/21211. PMID7839145.
↑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.
↑ 9.09.1Vore AP, Chang EH, Hoppe JE, Butler MG, Forrester S, Schneider MC, Smith LL, Burke DW, Campbell CA, Smith RJ (Dec 2005). "Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness". Archives of Otolaryngology–Head & Neck Surgery. 131 (12): 1057–63. doi:10.1001/archotol.131.12.1057. PMID16365218.
↑Choi BY, Kim DH, Chung T, Chang M, Kim EH, Kim AR, Seok J, Chang SO, Bok J, Kim D, Oh SH, Park WY (Feb 2013). "Destabilization and mislocalization of POU3F4 by C-terminal frameshift truncation and extension mutation". Human Mutation. 34 (2): 309–16. doi:10.1002/humu.22232. PMID23076972.
↑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.
de Kok YJ, Cremers CW, Ropers HH, Cremers FP (1997). "The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation". Human Mutation. 10 (3): 207–11. doi:10.1002/(SICI)1098-1004(1997)10:3<207::AID-HUMU5>3.0.CO;2-F. PMID9298820.
Phippard D, Heydemann A, Lechner M, Lu L, Lee D, Kyin T, Crenshaw EB (Jun 1998). "Changes in the subcellular localization of the Brn4 gene product precede mesenchymal remodeling of the otic capsule". Hearing Research. 120 (1–2): 77–85. doi:10.1016/S0378-5955(98)00059-8. PMID9667433.
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.
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.
