PMC6348282_01
a Family pedigree. The proband is indicated by an arrow (P). The patient had no family history of hearing loss or retinitis pigmentosa. b Absence of all waves in auditory brainstem response recording even at 105 dB in both ears of the patient (III:3) at the age of 1 year and 4 months compared with a healthy control (below) indicates severe bilateral hearing loss
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Fig1
The patient is a 12-year-old Japanese girl who is the third child of non-consanguineous parents with no family history of deafness or blindness (Fig. 1a). Her auditory brainstem response did not show any evoked responses below 100 decibel (dB) on both sides (Fig. 1b).
Partial sequence chromatograms for CDH23 in the patient and both parents. DNA and corresponding amino acid sequences of the wild-type and mutant CDH23 alleles are shown. Red arrows denote the sites of heterozygous sequences
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Fig2
Blood Institute Grand Opportunity (NHLBI GO) Exome Sequencing Project (ESP6500, http://evs.gs.washington.edu/EVS), Human Genetic Variation Database (http://www.genome.med.kyoto-u.ac.jp/SnpDB) and integrative Japanese Genome Variation Database (iJGVD, https://ijgvd.megabank.tohoku.ac.jp). TPS revealed compound heterozygous variants in CDH23 (NM_022124.5): one is paternally inherited c.130G>A in exon 3, and the other is maternally inherited c.945+1G>T in intron 10 (Fig. 2). Both of these variants were confirmed by trio Sanger sequencing.