Molecular diagnosis of non-syndromic hearing loss patients using a stepwise approach.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Deafness/*diagnosis ; Deafness/*genetics ; Genetic Testing/*methods; Child, Preschool ; China ; Female ; Genotype ; Hearing Loss/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Infant ; Infant, Newborn ; Male ; Multiplex Polymerase Chain Reaction/methods ; Mutation ; Pedigree ; Exome Sequencing/methods
    • Abstract:
      Hearing loss is one of the most common birth disorders in humans, with an estimated prevalence of 1-3 in every 1000 newborns. This study investigates the molecular etiology of a hearing loss cohort using a stepwise strategy to effectively diagnose patients and address the challenges posed by the genetic heterogeneity and variable mutation spectrum of hearing loss. In order to target known pathogenic variants, multiplex PCR plus next-generation sequencing was applied in the first step; patients which did not receive a diagnosis from this were further referred for exome sequencing. A total of 92 unrelated patients with nonsyndromic hearing loss were enrolled in the study. In total, 64% (59/92) of the patients were molecularly diagnosed, 44 of them in the first step by multiplex PCR plus sequencing. Exome sequencing resulted in eleven diagnoses (23%, 11/48) and four probable diagnoses (8%, 4/48) among the 48 patients who were not diagnosed in the first step. The rate of secondary findings from exome sequencing in our cohort was 3% (2/58). This research presents a molecular diagnosis spectrum of 92 non-syndromic hearing loss patients and demonstrates the benefits of using a stepwise diagnostic approach in the genetic testing of nonsyndromic hearing loss.
    • References:
      Genet Med. 2019 Nov;21(11):2614-2630. (PMID: 31171844)
      Genet Med. 2013 Jul;15(7):565-74. (PMID: 23788249)
      Genet Med. 2018 Dec;20(12):1600-1608. (PMID: 29595809)
      Nucleic Acids Res. 2015 Jan;43(Database issue):D670-81. (PMID: 25428374)
      JAMA. 2014 Nov 12;312(18):1870-9. (PMID: 25326635)
      Methods Mol Biol. 2012;838:311-28. (PMID: 22228019)
      N Engl J Med. 2017 Jan 5;376(1):21-31. (PMID: 27959697)
      Sci Rep. 2017 Dec 1;7(1):16783. (PMID: 29196752)
      Genet Test Mol Biomarkers. 2015 Jan;19(1):52-8. (PMID: 25493717)
      Genet Med. 2016 Apr;18(4):364-71. (PMID: 26226137)
      Clin Genet. 2020 Jul;98(1):32-42. (PMID: 32279305)
      Hum Genet. 2016 Apr;135(4):441-450. (PMID: 26969326)
      Mol Cytogenet. 2017 Aug 23;10:30. (PMID: 28852425)
      Genet Med. 2019 Oct;21(10):2409. (PMID: 31114025)
      J Transl Med. 2009 Apr 14;7:26. (PMID: 19366456)
      Mol Cell Probes. 2015 Oct;29(5):260-70. (PMID: 25845345)
      Hum Genet. 2020 Apr;139(4):521-530. (PMID: 32002660)
      Handb Clin Neurol. 2015;132:231-48. (PMID: 26564084)
      Genet Med. 2019 Oct;21(10):2231-2238. (PMID: 30890784)
      Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:61S-76S. (PMID: 25999548)
      Eur J Hum Genet. 2019 Feb;27(2):325-330. (PMID: 30291343)
      Science. 2016 Dec 23;354(6319):. (PMID: 28008009)
      Nat Genet. 2011 May;43(5):491-8. (PMID: 21478889)
      Nat Rev Dis Primers. 2017 Jan 12;3:16094. (PMID: 28079113)
      Am J Hum Genet. 2018 Sep 6;103(3):328-337. (PMID: 30100086)
      Genet Med. 2019 Nov;21(11):2442-2452. (PMID: 31160754)
      N Engl J Med. 2006 May 18;354(20):2151-64. (PMID: 16707752)
      Clin Genet. 2007 Sep;72(3):245-54. (PMID: 17718863)
      Hum Mutat. 2018 Nov;39(11):1593-1613. (PMID: 30311386)
      Eur J Hum Genet. 2017 Feb;25(3):308-314. (PMID: 28000701)
      Genome Res. 1999 Jan;9(1):7-16. (PMID: 9927480)
      Genet Med. 2019 Dec;21(12):2744-2754. (PMID: 31273342)
      Genet Med. 2018 Apr;20(5):536-544. (PMID: 29048421)
      Genome Med. 2014 May 22;6(5):37. (PMID: 24963352)
      Gigascience. 2017 May 1;6(5):1-9. (PMID: 28379488)
    • Grant Information:
      2016TX03R171 Special Foundation for High-level Talents of Guangdong
    • Subject Terms:
      Nonsyndromic Deafness
    • Publication Date:
      Date Created: 20210218 Date Completed: 20211221 Latest Revision: 20221207
    • Publication Date:
      20240513
    • Accession Number:
      PMC7889619
    • Accession Number:
      10.1038/s41598-021-83493-6
    • Accession Number:
      33597575