KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans
Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/15/1/48 |
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| author | Allison J. Kalinousky Teresa R. Luperchio Katrina M. Schrode Jacqueline R. Harris Li Zhang Valerie B. DeLeon Jill A. Fahrner Amanda M. Lauer Hans T. Bjornsson |
| author_facet | Allison J. Kalinousky Teresa R. Luperchio Katrina M. Schrode Jacqueline R. Harris Li Zhang Valerie B. DeLeon Jill A. Fahrner Amanda M. Lauer Hans T. Bjornsson |
| author_sort | Allison J. Kalinousky |
| collection | DOAJ |
| description | Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years. Our data suggest that while ear infections and structural abnormalities contribute to the observed hearing loss, these factors do not explain all loss. Using a KS1 mouse model, we found hearing abnormalities from hearing onset, as indicated by auditory brainstem response measurements. In contrast to mouse and human data for CHARGE syndrome, a disorder possessing overlapping clinical features with KS and a well-known cause of hearing loss and structural inner ear abnormalities, there are no apparent structural abnormalities of the cochlea in KS1 mice. The KS1 mice also display diminished distortion product otoacoustic emission levels, which suggests outer hair cell dysfunction. Combining these findings, our data suggests that KMT2D dysfunction causes sensorineural hearing loss compounded with external factors, such as infection. |
| first_indexed | 2024-03-08T10:54:27Z |
| format | Article |
| id | doaj.art-a1148e0baf784e7ebd4b8f0e54bfd2a3 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-08T10:54:27Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-a1148e0baf784e7ebd4b8f0e54bfd2a32024-01-26T16:41:41ZengMDPI AGGenes2073-44252023-12-011514810.3390/genes15010048KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and HumansAllison J. Kalinousky0Teresa R. Luperchio1Katrina M. Schrode2Jacqueline R. Harris3Li Zhang4Valerie B. DeLeon5Jill A. Fahrner6Amanda M. Lauer7Hans T. Bjornsson8McKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USAMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USADepartment of Otolaryngology-Head and Neck Surgery and Center for Hearing and Balance, Johns Hopkins School of Medicine, Baltimore, MD 21205, USAMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USAMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USADepartment of Anthropology, University of Florida, Gainesville, FL 32610, USAMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USADepartment of Otolaryngology-Head and Neck Surgery and Center for Hearing and Balance, Johns Hopkins School of Medicine, Baltimore, MD 21205, USAMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USAIndividuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years. Our data suggest that while ear infections and structural abnormalities contribute to the observed hearing loss, these factors do not explain all loss. Using a KS1 mouse model, we found hearing abnormalities from hearing onset, as indicated by auditory brainstem response measurements. In contrast to mouse and human data for CHARGE syndrome, a disorder possessing overlapping clinical features with KS and a well-known cause of hearing loss and structural inner ear abnormalities, there are no apparent structural abnormalities of the cochlea in KS1 mice. The KS1 mice also display diminished distortion product otoacoustic emission levels, which suggests outer hair cell dysfunction. Combining these findings, our data suggests that KMT2D dysfunction causes sensorineural hearing loss compounded with external factors, such as infection.https://www.mdpi.com/2073-4425/15/1/48Kabuki syndromecongenital hearing lossgenetic syndromehair cellsMLL2 |
| spellingShingle | Allison J. Kalinousky Teresa R. Luperchio Katrina M. Schrode Jacqueline R. Harris Li Zhang Valerie B. DeLeon Jill A. Fahrner Amanda M. Lauer Hans T. Bjornsson KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans Genes Kabuki syndrome congenital hearing loss genetic syndrome hair cells MLL2 |
| title | KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans |
| title_full | KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans |
| title_fullStr | KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans |
| title_full_unstemmed | KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans |
| title_short | KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans |
| title_sort | kmt2d deficiency causes sensorineural hearing loss in mice and humans |
| topic | Kabuki syndrome congenital hearing loss genetic syndrome hair cells MLL2 |
| url | https://www.mdpi.com/2073-4425/15/1/48 |
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