Zwaenepoel et al. (2002) were the first to report the presence of the otoancorin protein and the gene. The gene was found to localize to a position flanked by the markers D16S3046 and D16S409. The authors identified a consanguineous Palestinian family, in which moderate to severe prelingual sensorineural recessive deafness was shown to segregate with this locus (LOD score-3.56). Zwaenepoel et al. (2002) designed primers to amplify and sequence the OTOA gene in the patients. Sequence analysis enabled the identification of an IVS12+2T-C mutation in a homozygous condition in one child. This mutation was found to co-segregate with the disease phenotype in the family, and was not detected in 417 control individuals with normal hearing. Zwaenepoel et al. (2002) assumed that this mutation would lead to an aberrant splicing, such as exon 12 skipping, resulting in an in-frame deletion of 72 amino acids, or the use of a cryptic site. The authors concluded that OTOA was the causative gene for DFNB22.

Walsh et al. (2006) undertook a study to identify the genes responsible for inherited hearing loss, by linkage scan using microsatellite markers in 156 affected individuals and their families. The authors were able to identify a Palestinian family with mutation in the OTOA gene. Six members of this family were diagnosed with prelingual, bilateral, moderate to severe hearing loss. Five of them were found to be homozygous at markers D16S3045 and TTA (21.603), flanking OTOA. The sixth individual was heterozygous for D16S3045. Sequencing of the OTOA gene revealed a homozygous mutation 1067A-T (D356V) in all affected individuals. All unaffected members of the family were found to be either heterozygous carriers of this mutation or wild type. The mutation has been predicted to disrupt the transmembrane domain of the protein, thereby leading to loss of activity.

Shahin et al. (2010) carried out a molecular study to identify the genes responsible for inherited hearing loss, by using high-density SNP arrays to genotype the DNA of 155 relatives (including: 78 patients, 28 of their hearing siblings, and 49 parents) from 20 Palestinian consanguineous families with prelingual bilateral autosomal recessive non-syndromic hearing loss (NSHL). Shahin et al. (2010) identified a homozygous 500-kb deletion that resulted in complete deletion of the OTOA gene in affected sibs from one family. The parents were found to be heterozygous for this deletion. The deletion was flanked by segmental duplications at chromosome 16q, suggesting a mechanism of non-allelic homologous recombination. The deletion was observed in the heterozygous state in 3 (1.0%) of 288 unrelated Palestinian controls.