METHODS AND RESULTS: Whole exome sequencing was performed on 2 sisters with PDS and their unaffected parents. Our results showed that both sisters inherited monoallelic mutations in the 2 known PDS genes, SLC26A4 (ENST00000265715:c.1343C > T, p.Ser448Leu) and GJB2 (ENST00000382844:c.368C > A, p.Thr123Asn) from their father, as well as another deafness-related gene, SCARB2 (ENST00000264896:c.914C > T, p.Thr305Met) from their mother. We postulated that these three heterozygous mutations in combination may be causative to deafness, and warrants further investigation. Furthermore, we also identified a compound heterozygosity involving the DUOX2 gene (ENST00000603300:c.1588A > T:p.Lys530* and c.3329G > A:p.Arg1110Gln) in both sisters which are inherited from both parents and may be correlated with early onset of goiter. All the candidate mutations were predicted deleterious by in silico tools.
CONCLUSIONS: In summary, we proposed that PDS in this family could be a polygenic disorder which possibly arises from a combination of heterozygous mutations in SLC26A4, GJB2 and SCARB2 which associated with deafness, as well as compound heterozygous DUOX2 mutations which associated with thyroid dysfunction.
METHODS: Data from a retrospective review of 13-year S.suis patient records in a tertiary hospital in Chiang Mai, Northern, Thailand was obtained. Univariate and multivariate logistic regressions were employed to develop a predictive model. The clinical risk score was constructed from the coefficients of significant predictors. Area under the receiver operator characteristic curve (AuROC) was identified to verify the model discriminative performance. Bootstrap technique with 1000-fold bootstrapping was used for internal validation.
KEY RESULTS: Among 133 patients, the incidence of hearing loss was 31.6% (n = 42). Significant predictors for S. suis hearing loss were meningitis, raw pork consumption, and vertigo. The predictive score ranged from 0-4 and correctly classified 81.95% patients as being at risk of S.suis hearing loss. The model showed good power of prediction (AuROC: 0.859; 95%CI 0.785-0.933) and calibration (AuROC: 0.860; 95%CI 0.716-0.953).
CONCLUSIONS: To our best knowledge, this is the first risk scoring system development for S.suis hearing loss. We identified meningitis, raw pork consumption and vertigo as the main risk factors of S.suis hearing loss. Future studies are needed to optimize the developed scoring system and investigate its external validity before recommendation for use in clinical practice.