Molecular characterization of pathogenic OTOA gene conversions in hearing loss patients.
Hum Mutat
; 42(4): 373-377, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-33492714
ABSTRACT
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).
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Deafness
/
GPI-Linked Proteins
/
Hearing Loss
Limits:
Humans
Language:
En
Journal:
Hum Mutat
Year:
2021
Document type:
Article