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Background  Early-onset hearing loss is mostly of genetic origin. The complexity of the hearing process is reflected by its extensive genetic heterogeneity, with probably many causative genes remaining to be identified. Here, we aimed at identifying the genetic basis for autosomal dominant non-syndromic hearing loss (ADNSHL) in a large German family.    Methods  A panel of 66 known deafness genes was analyzed for mutations by next-generation sequencing (NGS) in the index patient. We then conducted genome-wide linkage analysis, and whole-exome sequencing was carried out with samples of two patients. Expression of Osbpl2 in the mouse cochlea was determined by immunohistochemistry. Because  Osbpl2  has been proposed as a target of  miR-96 , we investigated homozygous  Mir96  mutant mice for its upregulation.    Results  Onset of hearing loss in the investigated ADNSHL family is in childhood, initially affecting the high frequencies and progressing to profound deafness in adulthood. However, there is considerable intrafamilial variability. We mapped a novel ADNSHL locus,  DFNA67 , to chromosome 20q13.2-q13.33, and subsequently identified a co-segregating heterozygous frameshift mutation, c.141_142delTG (p.Arg50Alafs*103), in  OSBPL2 , encoding a protein known to interact with the  DFNA1  protein, DIAPH1. In mice, Osbpl2 was prominently expressed in stereocilia of cochlear outer and inner hair cells. We found no significant  Osbpl2  upregulation at the mRNA level in homozygous  Mir96  mutant mice.    Conclusion  The function of  OSBPL2  in the hearing process remains to be determined. Our study and the recent description of another frameshift mutation in a Chinese ADNSHL family identify  OSBPL2  as a novel gene for progressive deafness.    Electronic supplementary material  The online version of this article (doi:10.1186/s13023-015-0238-5) contains supplementary material, which is available to authorized users.

OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated in autosomal dominant hearing loss (DFNA67)