Dataset Information

A multiplex PCR amplicon sequencing assay to screen genetic hearing loss variants in newborns.

ABSTRACT:

Background

Congenital hearing loss is one of the most common birth defects. Early identification and management play a crucial role in improving patients' communication and language acquisition. Previous studies demonstrated that genetic screening complements newborn hearing screening in clinical settings.

Methods

We developed a multiplex PCR amplicon sequencing assay to sequence the full coding region of the GJB2 gene, the most pathogenic variants of the SLC26A4 gene, and hotspot variants in the MT-RNR1 gene. The sensitivity, specificity, and reliability were validated via samples with known genotypes. Finally, a pilot study was performed on 300 anonymous dried blood samples.

Results

Of 103 samples with known genotypes, the multiplex PCR amplicon sequencing assay accurately identified all the variants, demonstrating a 100% sensitivity and specificity. The consistency is high in the analysis of the test-retest reliability and internal consistency reliability. In the pilot study, 12.3% (37/300) of the newborns were found to carry at least one pathogenic variant, including 24, 10, and 3 from the GJB2, SLC26A4, and MT-RNR1 gene, respectively. With an allele frequency of 2.2%, the NM_004004.6(GJB2):c.109G>A was the most prevalent variant in the study population.

Conclusion

The multiplex PCR amplicon sequencing assay is an accurate and reliable test to detect hearing loss variants in the GJB2, SLC26A4, and MT-RNR1 genes. It can be used to screen genetic hearing loss in newborns.

SUBMITTER: Yang H

PROVIDER: S-EPMC7913202 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

A multiplex PCR amplicon sequencing assay to screen genetic hearing loss variants in newborns.

Yang Haiyan H Luo Hongyu H Zhang Guiwei G Zhang Junqing J Peng Zhiyu Z Xiang Jiale J

BMC medical genomics 20210227 1

<h4>Background</h4>Congenital hearing loss is one of the most common birth defects. Early identification and management play a crucial role in improving patients' communication and language acquisition. Previous studies demonstrated that genetic screening complements newborn hearing screening in clinical settings.<h4>Methods</h4>We developed a multiplex PCR amplicon sequencing assay to sequence the full coding region of the GJB2 gene, the most pathogenic variants of the SLC26A4 gene, and hotspot ...[more]

PMID: 33639928

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Project description:ImportanceHearing loss is a global social burden. Early identification of hearing loss missed by newborn hearing screening tests in the neonatal intensive care unit is crucial.ObjectiveTo assess the association between expanded genomic sequencing combined with hearing screening and detection of hearing loss as well as improvement in the neonatal intensive care unit.Design, setting, and participantsThis cohort study was performed between August 8, 2016, and December 31, 2020, among 8078 newborns admitted to the neonatal intensive care unit of the Children's Hospital of Fudan University in Shanghai, China. Follow-up for hearing status was performed via telephone interviews between September 1 and November 30, 2021.ExposuresA hearing screening test and the expanded genomic sequencing targeting 2742 genes were administered to each patient. Those who failed the hearing screening test or had positive genetic findings were referred for diagnostic audiometry at a median of 3 months of age.Main outcomes and measuresThe primary outcome was hearing loss missed by hearing screening test. Secondary outcomes were genetic findings and benefits associated with the expanded genomic sequencing for clinical management of patients in the neonatal intensive care unit.ResultsOf 8078 patients (4666 boys [57.8%]; median age, 6.3 days [IQR, 3.0-12.0 days]), 52 of 240 (21.7%) received a diagnosis of hearing loss. Expanded genomic sequencing combined with hearing screening was associated with a 15.6% increase (7 of 45 patients) in cases of diagnosed hearing loss that were missed by hearing screening. Of the 52 patients with hearing loss, genetic factors were identified for 39 patients (75.0%); GJB2 and SLC26A4 were the most common genes identified. Patients with genetic findings experienced a more severe degree of hearing loss than those without genetic findings (21 profound, 4 severe, 7 moderate, and 7 mild vs 2 severe, 4 moderate, and 7 mild; P = .005), with more bilateral hearing loss (39 of 39 [100%] vs 9 of 13 [69.2%]; P = .003). Clinical management strategies were changed for patients who underwent genomic sequencing combined with hearing screening.Conclusions and relevanceThis study suggests that expanded genomic sequencing combined with hearing screening may be effective at detecting hearing loss among patients in the neonatal intensive care unit.

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Dataset Information

A multiplex PCR amplicon sequencing assay to screen genetic hearing loss variants in newborns.

Background

Methods

Results

Conclusion

Publications

A multiplex PCR amplicon sequencing assay to screen genetic hearing loss variants in newborns.

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