While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with sensorineural hearing loss.
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We are grateful to the families participating in this study. This study was supported by R01DC09645 and R01DC012836 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders to MT and DNA/Tissue Bank of Akdeniz University, Antalya, Turkey.
As stated in human and animal sections above.
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Bademci, G., Abad, C., Incesulu, A. et al. MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss. Hum Genet 137, 479–486 (2018). https://doi.org/10.1007/s00439-018-1901-4