Table 1: Studies with UNHS and Concurrent Genetic Screening.
This table summarizes the 16 studies included in this review. After an extensive literature review, these studies analyzed the findings of infants who underwent UNHS and concurrent genetic screening.
| Title | Author | Year | Country of Origin | Number of Patients | Type of genetic testing | Genes Screened (Number of mutations) | UNHS Results (Pass/Fail) | Genetic Fail | Genetic Screen Results | UNHS pass/genetic fail % |
|---|---|---|---|---|---|---|---|---|---|---|
| Prevalence of A1555G mitochondrial mutation in Chinese newborns and the correlation with neonatal hearing screening | Chen et al. | 2011 | China | 865 | Direct sequencing | mtDNA 12s rRNA (mt1555G>A) | 84.5% (n=731)/15.5% (n=134) | 0.7% (n=6) | All homoplasmic mutations | 0.69 |
| GJB2-associated hearing loss undetected by hearing screening of newborns | Minami et al. | 2013 | Japan | 924 | Direct sequencing | GJB2 | 22.1% (204/924) with pathologic biallelic mutations. 18 different mutations identified | 1.5 | ||
| Newborn Genetic Screening for Hearing Impairment: A Preliminary Study at a Tertiary Center | Wu et al. | 2011 | Taiwan | 1017 | Next Generation Sequencing | GJB2 (2), SLC26A4 (1), mtDNA 12S rRNA (1) | 96.2%(n=979)/3.8% (n=38) | 19.6% (n=199) | 11 homozygous for GJB2 p.V37I, 6 compound heterozygous for GJB2 p.V37I and c.235delC, 1 homoplasmic for m.1555A.G. | 0.88 |
| Incidence of the 35delG/GJB2 mutation in low-risk newborns | Zaputovic et al. | 2008 | Croatia | 1048 | Direct sequencing | GJB2 (c.35delG mutation) | 99.7% (n=1045)/0.3% (n=3) | 1.3% (n=14) with mutation; 13/14 biallelic, 1/14 mono-allelic | 1.24 | |
| Evaluation of newborn screening bloodspot-based genetic testing as second tier screen for bedside newborn hearing screening | Schimmenti et al. | 2011 | United States | 2354 | Direct sequencing | GJB2 (c.35delG, c.167delT, c.235delC, and p.V37I mutations) | Case-control study with 50%/50% selected | 10.88% (n=139) | 0.98% (n=23) of all infants had bi-allelic GJB2 mutations, 9.9% (n=116) of all infants had mono-allelic mutations (carrier, not affected) | 0.04 |
| Newborn genetic screening for hearing impairment: a population-based longitudinal study | Wu et al. | 2016 | Taiwan | 5173 | Next Generation Sequencing | GJB2 (2), SLC26A4 (1), mtDNA 12S rRNA (1) | 94% (n=5008)/6% (n=165) | 16.2% (n=839 ) | 736 heterozygous for GJB2 p.V37I, 50 heterozygous for GJB2 c.235delC, 53 heterozygous for SLC26A4 c.919–2A>G). 82 (1.6%) babies with causative genotypes, 62 GJB2 p.V37I/p.V37I, 16 GJB2 p.V37I/c.235delC, 4 m.1555A>G | 0.89 |
| SNaPshot reveals high mutation and carrier frequencies of 15 common hearing loss mutants in a Chinese newborn cohort | Chen et al. | 2015 | China | 5800 | SNaPshot Multiplex System; Sanger sequencing | GJB2 (5), SLC26A4 (5), mtDNA 12s rRNA (5) | 15.9% (n=923) | GJB2 mutants accounted for up to 12.7% (735/5800). In addition, 2.17% (126/5800) had at least one mutant allele of SLC26A4, and 1.07% (62/5800) were carriers of a mitochondrial mutant allele. | 0.36 | |
| Newborn hearing screening and genetic testing in 8974 Brazilian neonates | Nivoloni et al. | 2010 | Brazil | 8974 | Direct sequencing | GJB2 (1), mtDNA 12s rRNA (2) | 99.8%(n=8957)/0.2%(n=17) | 84/8974 (0.94%) heterozygous for 35delG, 4/8974 (0.04%) homozygous for this mutation, no other GJB2 mutations found. Among 17 newborns who failed in TOAE, 4/17 were 35delG homozygous, confirming genetic etiology deafness (23.5%). 3/17 possessed 827A>G mtDNA mutation | ||
| Concurrent Genetic and Standard Screening for Hearing Impairment in 9317 Southern Chinese Newborns | Peng et al. | 2016 | China | 9317 | MALDI-TOF-MS PCR based array | GJB2 (5), GJB3 (2), SLC26A4 (11), mtDNA 12S rRNA (2) | 88.45% (n=8241)/11.55% (n=1076) | 3.74% of all infants (n=348) with at least 1 mutation. Only 0.36% (n=34) with causal mutation. | 310 heterozygous, 10 compound heterozygous, 28 homozygous. 30 mtDNA 12S rRNA, 1 GJB2 c.235delC homozyous, 3 SLC26A4 compound heterozygous. | 0.311 |
| Auditory screening concurrent deafness predisposing genes screening in 10,043 neonates in Gansu province, China | Zhang et al. | 2012 | China | 10043 | Restriction endonuclease; Direct sequencing | mtDNA 12sRNA, SLC26A4, GJB2 | 85.6%/14.4% | 2.29% (230/10,043) with at least 1 mutation | 21/230 genetically referred (18 mtDNA 12S rRNA mutation, 2 GJB2 c. [235delC] + [235- delC] homozygotes, 1 SLC26A4 c.[919–2A>G] + 12S rRNA 1555A>G compound type) | 1.91 |
| Newborn hearing concurrent gene screening can improve care for hearing loss: A study on 14,913 Chinese newborns | Wang et al. | 2011 | China | 14913 | Restriction endonuclease; Direct sequencing | mtDNA 12sRNA, SLC26A4, GJB2 | 86.1% (n=12,837)/13.9% (n=2073) | 2.1% (n=306) with at least 1 mutation | 26/306 were considered genetic refers (18 12S rRNA 1555A>G mutation, 5 GJB2 c.[235delC] + [235delC] homozygotes, 1 GJB2 c.[235delC] + [299delAT] compound heterozygote, 1 SLC26A4 c.[919–2A>G] + c.[2168 A>G] compound type, 1 compound type GJB2 c.[235delC] + SLC26A4 c.[919–2A>G]) | 0.13 |
| Government-funded universal newborn hearing screening and genetic analyses of deafness predisposing genes in Taiwan | Chu et al. | 2015 | Taiwan | 15345 | Direct sequencing | GJB2, GJB4, GJA1P1, GJB6, GJB3, GJA1, GJB1, GJC3, SLC26A4 | 97.32%(n=14934)/2.68%(n=411) | Only 26/32 with diagnosed hearing loss underwent genetic testing. Mutation detected in 38.5% (10/26). | 1 GJB3 c.580G>A, 1 GJB3 c.520G>A, 1 GJB2 c.235delC homozygote, 1 GJA1P1 c.929delC, 1 GJA1P1 novel variant c.1081C>T, 1 GJB4 c.302G>A, 1 GJA1 novel variant c.1–33C>G, 1 SLC26A4 c.919–2A>G + novel variant c.164+1G>C, 1 SLC26A4 c.919–2A>G, 1 SLC26A4 novel variant c.818C>T. | |
| Newborn hearing concurrent genetic screening for hearing impairment—A clinical practice in 58,397 neonates in Tianjin, China | Zhang et al. | 2013 | China | 58397 | MALDI-TOF-MS PCR based array | GJB2 (5), GJB3 (2), SLC26A4 (11), mtDNA 12s rRNA (2) | 89.1%(n=52020)/10.9%(n=6377) | 5.52% (n=3225) with at least one mutated allele | 0.25% (n=143) were referred (biallelic non carrier mutation) due to mitochondrial, homozygous GJB2, or homozygous SLC26A4 mutations. 5.28% (n=3082) infants were genetic mutation carriers. | 0.19 |
| Prenatal Diagnosis of SLC26A4 Mutation and Delayed Onset of Hearing Loss | Iwata et al. | 2012 | United States | 1 HL | Direct sequencing | SLC26A4 mutations G316X and 918–2A>G | Passed | Positive for both SLC26A4 mutations G316X and 918–2A>G | 100 | |
| Utility of Genetic Testing for the Detection of Late-Onset Hearing Loss in Neonates | Lim et al. | 2013 | United States | 3681 NSHL | SoundGene Panel | GJB6 deletion, GJB2 (4), SLC26A4 (4), mtDNA 12s rRNA (5); CMV PCR | 99.6% (n=3667)/0.14% (n=14) | 7.0% of all infants (n=259) with a mutation. Only 0.95% (n=35) with positive SoundGene panel | 1 GJB2, 16 mtDNA 12s rRNA, 10 SLC26A4, 3 compound heterozygote, 5 CMV. | 0.9 |
| Limitations of hearing screening in newborns with PDS mutations | Kim et al. | 2012 | Korea | 43 SNHL | Direct sequencing | SLC26A4 | All neonates with PDS pendrin mutation | 28.5 |