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Human Genetics

, Volume 135, Issue 4, pp 441–450

First Online: 11 March 2016Received: 16 December 2015Accepted: 14 February 2016


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 <1 %. The diagnostic rate varied considerably based on phenotype and was highest for patients with a positive family history of hearing loss or when the loss was congenital and symmetric. The spectrum of implicated genes showed wide ethnic variability. These findings support the more efficient utilization of medical resources through the development of evidence-based algorithms for the diagnosis of hearing loss.

A. O. Bierer, A. E. Shearer, and D. L. Kolbe all contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00439-016-1648-8 contains supplementary material, which is available to authorized users.

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Autor: Christina M. Sloan-Heggen - Amanda O. Bierer - A. Eliot Shearer - Diana L. Kolbe - Carla J. Nishimura - Kathy L. Frees


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