Frequency and specific characteristics of the incomplete partition type III anomaly in children
Ayako Kanno MD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Department of Otolaryngology, Inagi Municipal Hospital, Tokyo, Japan
Department of Otolaryngology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorHideki Mutai DVM, PhD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Search for more papers by this authorKazunori Namba PhD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Search for more papers by this authorNoriko Morita MD, PhD
Department of Otolaryngology, Kobari General Hospital, Chiba, Japan
Search for more papers by this authorAtsuko Nakano MD, PhD
Division of Otolaryngology, Chiba Children's Hospital, Chiba, Japan
Search for more papers by this authorNoboru Ogahara MD, PhD
Department of Otorhinolaryngology, Kanagawa Children's Medical Center, Kanagawa, Japan
Search for more papers by this authorTomoko Sugiuchi MD, PhD
Department of Otolaryngology, Kanto Rosai Hospital, Kanagawa, Japan
Search for more papers by this authorKaoru Ogawa MD, PhD
Department of Otolaryngology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Tatsuo Matsunaga MD, PhD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Medical Genetics Center, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Send correspondence to Tatsuo Matsunaga, MD, PhD, 2-5-1 Higashigaoka, Meguro, Tokyo 152-8902, Japan. E-mail: [email protected]Search for more papers by this authorAyako Kanno MD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Department of Otolaryngology, Inagi Municipal Hospital, Tokyo, Japan
Department of Otolaryngology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorHideki Mutai DVM, PhD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Search for more papers by this authorKazunori Namba PhD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Search for more papers by this authorNoriko Morita MD, PhD
Department of Otolaryngology, Kobari General Hospital, Chiba, Japan
Search for more papers by this authorAtsuko Nakano MD, PhD
Division of Otolaryngology, Chiba Children's Hospital, Chiba, Japan
Search for more papers by this authorNoboru Ogahara MD, PhD
Department of Otorhinolaryngology, Kanagawa Children's Medical Center, Kanagawa, Japan
Search for more papers by this authorTomoko Sugiuchi MD, PhD
Department of Otolaryngology, Kanto Rosai Hospital, Kanagawa, Japan
Search for more papers by this authorKaoru Ogawa MD, PhD
Department of Otolaryngology, Keio University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Tatsuo Matsunaga MD, PhD
Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Medical Genetics Center, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
Send correspondence to Tatsuo Matsunaga, MD, PhD, 2-5-1 Higashigaoka, Meguro, Tokyo 152-8902, Japan. E-mail: [email protected]Search for more papers by this authorThis work was supported by a Health and Labor Sciences Research grant (Research on Rare and Intractable Diseases; H26-nanchitou-ippan-035) from the Ministry of Health Labor and Welfare of Japan, and a Grant-in-Aid for Clinical Research (H27-NHO [kankaku]-02) from the National Hospital Organization.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Abstract
Objectives/Hypothesis
To determine the frequency of the incomplete partition type III anomaly and the genetic and clinical features associated with POU3F4 mutations in children with hearing loss.
Study Design
Retrospective case series from 2000 to 2014 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals.
Methods
A total of 1,004 patients (from 938 families) who had hearing loss by 10 years of age and had undergone computed tomography scanning of their temporal bones were enrolled in this genetic, clinical, and radiological study.
Results
The incomplete partition type III anomaly was identified in six patients (0.6%), each of whom had an enlargement of the vestibular aqueduct at the end close to the vestibule. The six patients also had POU3F4 variants, and a genetic analysis revealed frameshift deletions in three patients, a missense variant in two patients of the same family, and a large deletion in one patient. Three of the six patients with POU3F4 variants were sporadic cases, and in one patient the genetic mutation occurred de novo.
Conclusions
It was indicated that POU3F4 mutations can be predicted by incomplete partition type III anomaly by radiological examination of the inner ear. All six of the patients showed mixed hearing loss, but none showed fluctuations in hearing, which may be related to the lack of vestibular aqueduct enlargement at the operculum.
Level of Evidence
4 Laryngoscope, 127:1663–1669, 2017
Supporting Information
Additional supporting information can be found in the online version of this article.
| Filename | Description |
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| lary26245-sup-0001-suppinfo.docx21.8 KB | Supporting Information |
| lary26245-sup-0002-suppinfoFigS1.jpg1.5 MB | Supporting Fig. 1. JPEG format (.jpg) Hydrogen bonds between the DNA-binding site for POU3F4 and the palindromic MORE DNA. (a) Sequences of DNA-binding site for POU3F4 (top) and the template mouse Pou3f1 (middle) are aligned with the schematic topology representing seven helices (waves S1-S7, bottom). Amino acids identical to Pou3f1 are highlighted in orange. Amino acids shown or predicted to interact with DNA by hydrogen bonds are highlighted in red. The position of Q331 is indicated by a black arrow. (b) Predicted hydrogen bonds between the palindromic MORE DNA and POU3F4 are indicated by light blue arrows together with the amino acid residues and the positions. Number of hydrogen bonds from each side chain of amino acid is shown in red with brackets. |
| lary26245-sup-0003-suppinfoFigS2.jpg345.8 KB | Supporting Fig. 2. MS Powerpoint format (.pptx) Auditory assessment of each patient. (a, g, h) Conditional orientation audiometry results. (b–f, i, j) PTA results. |
| lary26245-sup-0004-suppinfoTabS1.jpg127.5 KB | Supporting Information Table S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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