title: Audiological and surgical evidence for the presence of a third window effect for the conductive hearing loss in DFNX2 deafness irrespective of types of mutations.
abstract: The objective of this study was to clarify the cause of the air-bone gap in incomplete partition (IP) type III cases according to the POU3F4 gene (DFNX2) mutation type. A retrospective analysis of patient medical records was done in a tertiary referral medical center. Five IP type III patients proved to be carrying a mutation in or affecting POU3F4. The hearing and the middle ear status at either exploratory tympanotomy or cochlear implantation from these DFNX2 cases was reviewed. Four of five unrelated IP type III patients harbored a point mutation of POU3F4 and the fifth patient carried a large genomic deletion upstream to POU3F4. Two of the four DFNX2 patients carrying a point mutation had moderate to severe mixed hearing loss with a substantial amount of air-bone gap. These patients underwent exploratory tympanotomy to identify the cause of their hearing loss. The other three patients, including one carrying a large deletion, had profound hearing loss at presentation and received a cochlear implant. In the exploratory tympanotomy group with a substantial amount of air-bone gap and a point mutation (n = 2), one patient had a perfect ossicular chain with normal mobility, a positive ipsilateral stapedial reflex, and a positive round window reflex. In the cochlear implantation group (n = 3), we found a stapes with normal mobility and a positive round window reflex in one patient who harbored a large genomic deletion upstream to POU3F4. We concluded that the probable presence of the third window effect is not limited to the particular type of POU3F4 mutation.
authors: Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, Korea, choiby@snubh.org.
authors: Byung Yoon
authors: BY
authors: Choi
authors: Yong-Hwi
authors: YH
authors: An
authors: Joo Hyun
authors: JH
authors: Park
authors: Jeong Hun
authors: JH
authors: Jang
authors: Hyun Chung
authors: HC
authors: Chung
authors: Ah-Reum
authors: AR
authors: Kim
authors: Jun Ho
authors: JH
authors: Lee
authors: Chong-Sun
authors: CS
authors: Kim
authors: Seung Ha
authors: SH
authors: Oh
authors: Sun O
authors: SO
authors: Chang
mesh_terms: D001301:Audiometry, Pure-Tone; D002648:Child; D002675:Child, Preschool; D003054:Cochlear Implants; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D006314:Hearing Loss, Conductive / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology* / Q000601:surgery*; D006801:Humans; D007223:Infant; D008297:Male; D050809:POU Domain Factors / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D014432:Tympanic Membrane / Q000601:surgery
chemical_list: D050809:POU Domain Factors; C091774:POU3F4 protein, human
references: Am J Otol. 1985 May;6(3):243-6
references: 4039896
references: Otol Neurotol. 2006 Aug;27(5):615-23
references: 16788416
references: Neuroradiology. 1991;33(4):326-30
references: 1922747
references: Hum Mol Genet. 1996 Sep;5(9):1229-35
references: 8872461
references: Arch Otolaryngol. 1985 Apr;111(4):249-54
references: 3977755
references: Birth Defects Orig Artic Ser. 1971 Mar;07(4):64-9
references: 5173351
references: Adv Otorhinolaryngol. 2002;61:161-7
references: 12408080
references: Otol Neurotol. 2008 Apr;29(3):282-9
references: 18223508
references: Arch Otorhinolaryngol. 1977 Jan 19;214(3):271-82
references: 576408
references: Science. 1995 Feb 3;267(5198):685-8
references: 7839145
references: Am J Otol. 1995 Mar;16(2):241-6
references: 8572127
references: Hum Mol Genet. 1994 Jul;3(7):1151-4
references: 7981685
references: Arch Otolaryngol. 1973 Aug;98(2):82-91
references: 4723769
references: Eur Arch Otorhinolaryngol. 2008 Nov;265(11):1425-30
references: 18305951
references: Clin Genet. 2009 Jun;75(6):572-5
references: 19438930