Abstract
BackgroundCongenital hearing loss affects approximately 1–2 infants out of every 1000, with 50% of the cases resulting from genetic factors. Targeted gene panels have been widely used for genetic diagnosis of hearing loss. This study aims to reveal new diagnoses via reanalyzing historical data of a multigene panel, and exam the reasons for new diagnoses.MethodsA total of 210 samples were enlisted, including clinical reports and sequencing data of patients with congenital/prelingual hearing loss who were referred to clinical genetic testing from October 2014 to June 2017. All variants listed on the original clinical reports were reinterpreted according to the standards and guidelines recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). Expanded analysis of raw data were performed in undiagnosed cases.ResultsRe-analysis resulted in nine new diagnoses, improving the overall diagnostic rate from 39 to 43%. New diagnoses were attributed to newly published clinical evidence in the literature, adoption of new interpretation guidelines and expanded analysis range.ConclusionThis work demonstrates benefits of reanalysis of targeted gene panel data, indicating that periodical reanalysis should be performed in clinical practice.
Highlights
Congenital hearing loss affects approximately 1–2 infants out of every 1000, with 50% of the cases resulting from genetic factors [1]
Sanger sequencing diagnoses usually begin by testing a limited number of selected genes, resulting in a low detection rate [3]; well-established genetic knowledge about the target
Patients A total of 210 patients with congenital or prelingual hearing loss, defined as detection before three years of age, were retrospectively studied. They had been referred to clinical genetic testing from October 2014 to June 2017 and consented to anonymous use of their data for scientific research
Summary
Congenital hearing loss affects approximately 1–2 infants out of every 1000, with 50% of the cases resulting from genetic factors. One of the molecular testing methods used to diagnose hearing loss is Sanger sequencing. Sanger sequencing diagnoses usually begin by testing a limited number of selected genes (generally starting with GJB2 in hearing loss), resulting in a low detection rate [3]; well-established genetic knowledge about the target. With the advance of generation sequencing (NGS) techniques, targeted genomic capture and massively parallel sequencing has become an important diagnostic tool for hereditary hearing loss [5]. This method can be used to examine over one hundred known deafness-related genes simultaneously. The diagnostic yield of comprehensive NGS hearing loss testing panels is close to 40% [4, 6], much higher than that of Sanger sequencing
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