Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss

• Published in: Human genetics 2016-04, Vol.135 (4), p.441-450
• Main Authors: Sloan-Heggen, Christina M., Bierer, Amanda O., Shearer, A. Eliot, Kolbe, Diana L., Nishimura, Carla J., Frees, Kathy L., Ephraim, Sean S., Shibata, Seiji B., Booth, Kevin T., Campbell, Colleen A., Ranum, Paul T., Weaver, Amy E., Black-Ziegelbein, E. Ann, Wang, Donghong, Azaiez, Hela, Smith, Richard J. H.
• Format: Article
• Language: English
• Subjects: Adolescent; Biomedical and Life Sciences; Biomedicine; Child; Child, Preschool; Ethnicity; Female; Gene Function; Genetic counseling; Genetic Heterogeneity; Genetic Testing; Genotype & phenotype; Hearing loss; Hearing Loss - diagnosis; Hearing Loss - genetics; Hearing protection; Human Genetics; Humans; Infant; Laboratories; Male; Metabolic Diseases; Molecular Medicine; Original Investigation; Otolaryngology; Patients
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-016-1648-8

Hearing loss is the most common sensory deficit in humans, affecting 1 in 500 newborns. Due to its genetic heterogeneity, comprehensive diagnostic testing has not previously been completed in a large multiethnic cohort. To determine the aggregate contribution inheritance makes to non-syndromic hearing loss, we performed comprehensive clinical genetic testing with targeted genomic enrichment and massively parallel sequencing on 1119 sequentially accrued patients. No patient was excluded based on phenotype, inheritance or previous testing. Testing resulted in identification of the underlying genetic cause for hearing loss in 440 patients (39 %). Pathogenic variants were found in 49 genes and included missense variants (49 %), large copy number changes (18 %), small insertions and deletions (18 %), nonsense variants (8 %), splice-site alterations (6 %), and promoter variants (