Bi-allelic loss-of-function variants of OTOA are a well-known
cause of moderate-to-severe 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 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 polymerase chain reactions.
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 stretches
of converted DNA of widely different lengths (at least 9 kbp and around
900 bp,
respectively).
Molecular characterization of pathogenic
OTOA
gene conversions in hearing loss patients
