Figure 1.
Schematic flow chart of this study.
An initial cohort of 201 families underwent genetic studies. Among them, subjects with nonsyndromic SNHL (sensorineural hearing loss) and autosomal recessive (AR) or sporadic inheritance patterns were selected. Based on the degree of hearing loss, final cohorts were classified into two groups: slight, mild or moderate SNHL (group I); severe or profound SNHL (group II).
Table 1.
Differences in prevalence of p.V37I variant and inheritance patterns.
Figure 2.
Three families with the p.V37I variant and moderate or slight hearing loss.
Two subjects (SH42-94, SB51-95) carried the p.V37I allele in a trans configuration with another mutant allele of GJB2, as a compound heterozygote and the other subject (SB80-141) carried the p.V37I allele as the only variant. (A) Detailed data of each subject’s pure tone audiometry at their initial visit. (B) Detailed data of each subject’s pedigree and Sanger sequencing traces. Next generation sequencing trace of p.V37I variant of GJB2 from two subjects (SH42-94, SB51-95) are shown. The Auditory Steady-State Response (ASSR) result of SB80-141 at the initial visit is shown due to poor cooperation in pure tone audiometry test.
Figure 3.
Progressive hearing loss shown in a family.
(A) Pure tone audiometry (at initial visit, and at follow up visit 5 months later) (B) Subjects’ pedigree and (C) Sanger sequencing traces are shown. Rapid progression of hearing loss over 5 months was noted in SHJ12 carrying the p.V37I and p.R143W mutant alleles.
Figure 4.
Multiplex breakpoint PCR to detect del(GJB6-D13S1830) and del(GJB6-D13S1854) ) from two single heterozygous carriers of p.V37I (SHJ1 and SB80-141).
A 564 bp band and a 460 bp band, indicative of the amplification of the del (GJB6-D13S1854) breakpoint junction and del (GJB6-D13S1830) breakpoint junction, respectively, were absent in SHJ1 and SB 80–141, despite a positive band being amplified from the control region, GJB6 exon 1.
Table 2.
Variants detected by targeted next generation sequencing of 82 deafness genes from two subjects (SH42-94, SB51-95) carrying p.V37I variant of GJB2.