Figure 8. Isoleucine deletion in the transmembrane domain of otoferlin causes impaired ER targeting in vitro and hearing impairment in a human patient.

1. Electropherograms of the sequences containing the mutations observed in family E952. Position within the OTOF cDNA (NM_001287489.1) is indicated above each sequence. For each mutation, the wild‐type sequence and the heterozygous sequence are shown. For purposes of clarity, the two alleles carried by subject E952‐II:1 were subcloned into a plasmid vector and sequenced in separation. Sequences of the subcloned mutant alleles are shown in the bottom row.
2. Pedigree of family E952 showing the segregation of mutations in the OTOF gene.
3. Apparent decrease in insertion efficiency for the TMD mutant version. While the WT otoferlin glycosylation amounted to 3.84 ± 0.53, the TMD mutant had only 2.13 ± 0.65 (n = 3, *P < 0.05). Data are represented as means ± SEM.

Source data are available online for this figure.