Table 3.
Participants in the NC NEXUS Hearing Loss Cohort with Positive or Inconclusive Findings
| NC NEXUS Participant | NGS-NBS Result | Diagnostic (Dx) Result | Gene(s) | Disease Association with Gene (Inheritance) | Variant and (Predicted Protein Change) | Zygosity in NC NEXUS Participant |
|---|---|---|---|---|---|---|
| HL003 | abnormal | positive | SLC26A4 | Pendred syndrome (AR) | c.626G>T (p.Gly209Val); c.1151A>G (p.Glu384Gly) | heterozygous for both variants |
| HL004 | normal | inconclusive VUS | MARVELD2 MYO7A | deafness 49 (AR); deafness 2 (AR); Usher type 1B (AR) | MARVELD2 c.1183−1G>A (p.?); MYO7A c.5824G>A (p.Gly1942Arg) | heterozygous for MARVELD2 variant; homozygous for MYO7A variant |
| HL010 | abnormal | positive | USH2A | Usher type 2A (AR) | c.1256G>T (p.Cys419Phe); c.3686T>G (p.Leu1229∗) | heterozygous for both variants |
| HL013 | abnormal | negative | F11 | factor XI deficiency (AR) | c.1489C>T (p.Arg497∗); c.1608G>C (p.Lys536Asn) | heterozygous for both variants |
| HL014 | abnormal | positive | GJB2 | deafness 1A (AR) | c.35del (p.Gly12fs) | homozygous |
| HL016 | abnormal | positive | USH2A | Usher type 2A (AR) | c.4338_4339del (p.Cys1447fs); c.2299del (p.Glu767fs) | heterozygous for both variants |
| HL017 | abnormal | positive | TECTA | deafness 8/12 (AD) | c.5597C>T (p.Thr1866Met) | heterozygous |
| HL021 | abnormal | negative | DSC2 | arrhythmogenic right ventricular dysplasia (ARVD11) (AD) | c.631−2A>G (p.?) | heterozygous |
| HL022 | normal | inconclusive VUS | TMPRSS3 | nonsyndromic hearing loss and deafness (AR) | c.208del (p.His70fs); c.1151T>A (p.Met384Lys) | heterozygous for both variants |
| HL025 | normal | inconclusive (heterozygous variant) | GJB2 | deafness (AR) | c.35del (p.Gly12fs) | heterozygous |
| HL026 | normal | inconclusive VUS | LOXHD1; CEMIP; MYH14 | hearing loss (AR or AD) | LOXHD1 c.2914G>A (p.Glu972Lys); LOXHD1 c.3161C>T (p.Thr1054Met); CEMIP/KIAA1199 c.58C>T (p.Leu20Phe); MYH14 c.5942G>C (p.Gly1981Ala) | heterozygous for all variants |
| HL027 | normal | inconclusive VUS | SOX10 | Waardenburg syndrome (AD) | c.482G>A (p.Arg161His) | heterozygous |
The NC NEXUS participant column includes “HL” (indicating hearing loss cohort) followed by the participant number. Each row in the table represents one NC NEXUS participant. An abnormal NGS-NBS result was indicated by a likely pathogenic or pathogenic variant found in the newborn screen gene list. A positive diagnostic result was indicated by a likely pathogenic or pathogenic variant found in a gene on the hearing loss list. An inconclusive diagnostic result was indicated by any variant of uncertain significance (VUS) finding or a heterozygous variant found in a gene associated with an autosomal-recessive form of hearing loss. A negative diagnostic result indicated we did not detect any pathogenic or likely pathogenic variants or any VUS on the hearing loss gene list. Gene symbols are italicized. NGS-NBS, next-generation sequencing newborn screen; AR, autosomal-recessive pattern of inheritance; AD, autosomal-dominant pattern of inheritance.