Suspension array-based deafness genetic screening in 53,033 Chinese newborns identifies high prevalence of 109 G>A in GJB2.

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  • Additional Information
    • Source:
      Publisher: Elsevier Scientific Publishers Country of Publication: Ireland NLM ID: 8003603 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8464 (Electronic) Linking ISSN: 01655876 NLM ISO Abbreviation: Int J Pediatr Otorhinolaryngol Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : Elsevier Scientific Publishers
      Original Publication: [Amsterdam] Elsevier/North-Holland.
    • Subject Terms:
      Genetic Testing* ; Mutation* ; Neonatal Screening*; Connexins/*genetics ; Deafness/*genetics ; Oligonucleotide Array Sequence Analysis/*methods; Asian People/genetics ; China/epidemiology ; Connexin 26 ; Deafness/congenital ; Deafness/epidemiology ; Female ; Gene Frequency ; Heterozygote ; Homozygote ; Humans ; Infant, Newborn ; Male ; Mitochondria/genetics ; Prevalence ; RNA, Ribosomal/genetics ; Sulfate Transporters/genetics
    • Abstract:
      Objectives: More than 50% of congenital hearing loss is attributed to genetic factors. Data of gene mutation associated with hearing loss from large population studies in Chinese population are scarce. In this study, we conducted a comprehensive newborn genetic screening in China to establish the carrier frequency and mutation spectrum of deafness-associated genes.
      Methods: A total of 53,033 newborns were screened for hearing defects associated mutations. Twenty hot spot mutations in GJB2, GJB3, SLC26A4 and mitochondria12S rRNA were examined using suspension array analysis.
      Results: 14,185 newborns (26.75%) were identified with at least one mutated allele. 872 (1.64%) neonates carried homozygous mutations including 112 (0.21%) mitochondrial DNA homoplasmy, 228 (0.43%) were compound heterozygotes, and 11,985 (22.59%) were heterozygotes including 11 (0.02%) mitochondrial DNA heteroplasmy. Top five mutations included 109 G > A, 235 delC, 299-300 delAT in GJB2, IVS7-2 A > G in SLC26A4 and 1555 A > G in mitochondria12S rRNA. Notably, a total of 10,995 neonates (20.73%) carried 109 G > A in GJB2. Moreover, the allele frequencies of 109 G > A were detected 11.61% in Guangdong, 10.44% in Sichuan and 2.88% in Shandong, respectively, a significant difference in prevalence among these geographic regions (p<0.01). In addition, the high frequency of 109 G > A in GJB2 was confirmed by a TaqMan probe-based qPCR assay. Very recently, the ClinGen Hearing Loss Expert Panel reached a consensus and confirmed its pathogenic role in hearing impairment.
      Conclusion: We delineated the mutation profile of common deafness-causing genes in the Chinese population and highlighted the high prevalence of 109 G > A pathogenic mutation. Our study may facilitate early diagnosis/intervention and genetic counseling for hearing impairment in clinical practice.
      (Copyright © 2019 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Gene mutation; Genetic screening; Hearing impairment; Suspension array
    • Accession Number:
      0 (Connexins)
      0 (GJB2 protein, human)
      0 (RNA, Ribosomal)
      0 (RNA, ribosomal, 12S)
      0 (SLC26A4 protein, human)
      0 (Sulfate Transporters)
      127120-53-0 (Connexin 26)
      136362-16-8 (GJB3 protein, human)
    • Publication Date:
      Date Created: 20190824 Date Completed: 20200206 Latest Revision: 20221207
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/j.ijporl.2019.109630
    • Accession Number:
      31442870