Bi-allelic loss-of-function variants of OTOA are a well-known
cause of mild-to-moderate hearing loss. Whereas non-allelic homologous
recombination-mediated deletions of the gene are well known, gene
conversions to pseudogene OTOAP1 have been reported in the
literature but never fully described nor their pathogenicity assessed.
Here, we report two unrelated patients with mild-to-moderate
hearing-loss, who were compound heterozygotes for a converted allele and
a deletion of OTOA. The conversions were initially detected
through sequencing depths anomalies at the OTOA locus after exome
sequencing, then confirmed with long range PCRs. Both conversions lead
to loss-of-function by introducing a premature stop codon in exon 22
(p.Glu787*). Using genomic alignments and long read nanopore sequencing,
we found that the two probands carry converted alleles of widely
different lengths, suggesting that they originated from different
mechanisms of gene conversion.