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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Bibliographic Details
Published in:Genes 2024-01, Vol.15 (1), p.48
Main Authors: Kalinousky, Allison J, Luperchio, Teresa R, Schrode, Katrina M, Harris, Jacqueline R, Zhang, Li, DeLeon, Valerie B, Fahrner, Jill A, Lauer, Amanda M, Bjornsson, Hans T
Format: Article
Language:English
Subjects:
Abnormalities, Multiple
Animals
Brain stem
Causality
CHARGE Syndrome
Child
Children
Cochlea
Congenital defects
Deafness
DNA methylation
Epigenetics
Ethylenediaminetetraacetic acid
Face - abnormalities
Genes
Genotype & phenotype
Health aspects
Hearing
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing protection
Hematologic Diseases
Humans
Immunodeficiency
Infection
Inner ear
Medical colleges
Mice
Noise
Phenotypes
Software
Sound
Variance analysis
Vestibular Diseases
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Summary: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.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes15010048