High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population
To decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2020/5625768 |
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| author | Hongyang Wang Dan Bing Jin Li Linyi Xie Fen Xiong Lan Lan Dayong Wang Jing Guan Qiuju Wang |
| author_facet | Hongyang Wang Dan Bing Jin Li Linyi Xie Fen Xiong Lan Lan Dayong Wang Jing Guan Qiuju Wang |
| author_sort | Hongyang Wang |
| collection | DOAJ |
| description | To decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations were recruited and identified by Sanger sequencing or next-generation sequencing; the participants included 30 patients from 16 reported families and 20 new cases. We found that AIFM1-positive cases accounted for 18.6% of late-onset AN cases. Of the 50 AN patients with AIFM1 variants, 45 were male and 5 were female. The hotspot variation of this gene was p.Leu344Phe, accounting for 36.1%. A total of 19 AIFM1 variants were reported in this study, including 7 novel ones. A follow-up study was performed on 30 previously reported AIFM1-positive subjects, 16 follow-up cases (53.3%) were included in this study, and follow-up periods were recorded from 1 to 23 years with average 9.75±9.89 years. There was no hearing threshold increase during the short-term follow-up period (1-10 years), but the low-frequency and high-frequency hearing thresholds showed a significant increase with the prolongation of follow-up time. The speech discrimination score progressed gradually and significantly along with the course of the disease and showed a more serious decline, which was disproportionately worse than the pure tone threshold. In addition to the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is also observed in AIFM1-related AN and affects females. In conclusion, we confirmed that AIFM1 is the primary related gene among late-onset AN cases, and the most common recurrent variant is p.Leu344Phe. Except for the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is another probability of AIFM1-related AN, with females affected. Phenotypical features of AIFM1-related AN suggested that auditory dyssynchrony progressively worsened over time. |
| format | Article |
| id | doaj-art-27316311c1614b3e8efd16d907b2c3bf |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-27316311c1614b3e8efd16d907b2c3bf2025-02-03T00:58:42ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/56257685625768High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese PopulationHongyang Wang0Dan Bing1Jin Li2Linyi Xie3Fen Xiong4Lan Lan5Dayong Wang6Jing Guan7Qiuju Wang8College of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaCollege of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaCollege of Otolaryngology, Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, ChinaTo decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations were recruited and identified by Sanger sequencing or next-generation sequencing; the participants included 30 patients from 16 reported families and 20 new cases. We found that AIFM1-positive cases accounted for 18.6% of late-onset AN cases. Of the 50 AN patients with AIFM1 variants, 45 were male and 5 were female. The hotspot variation of this gene was p.Leu344Phe, accounting for 36.1%. A total of 19 AIFM1 variants were reported in this study, including 7 novel ones. A follow-up study was performed on 30 previously reported AIFM1-positive subjects, 16 follow-up cases (53.3%) were included in this study, and follow-up periods were recorded from 1 to 23 years with average 9.75±9.89 years. There was no hearing threshold increase during the short-term follow-up period (1-10 years), but the low-frequency and high-frequency hearing thresholds showed a significant increase with the prolongation of follow-up time. The speech discrimination score progressed gradually and significantly along with the course of the disease and showed a more serious decline, which was disproportionately worse than the pure tone threshold. In addition to the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is also observed in AIFM1-related AN and affects females. In conclusion, we confirmed that AIFM1 is the primary related gene among late-onset AN cases, and the most common recurrent variant is p.Leu344Phe. Except for the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is another probability of AIFM1-related AN, with females affected. Phenotypical features of AIFM1-related AN suggested that auditory dyssynchrony progressively worsened over time.http://dx.doi.org/10.1155/2020/5625768 |
| spellingShingle | Hongyang Wang Dan Bing Jin Li Linyi Xie Fen Xiong Lan Lan Dayong Wang Jing Guan Qiuju Wang High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population Neural Plasticity |
| title | High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population |
| title_full | High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population |
| title_fullStr | High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population |
| title_full_unstemmed | High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population |
| title_short | High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population |
| title_sort | high frequency of aifm1 variants and phenotype progression of auditory neuropathy in a chinese population |
| url | http://dx.doi.org/10.1155/2020/5625768 |
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