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Topics {✒️}

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         headline:Genetic analysis of patients with low-frequency non-syndromic hearing loss
         description:Low-frequency non-syndromic hearing loss (LFNSHL) is a rare auditory disorder affecting frequencies ≤ 2000 Hz. To elucidate its genetic basis, we conducted whole-exome sequencing on nine Chinese families (31 affected individuals) with LFNSHL. Four heterozygous pathogenic variants, including two novel variants, were identified in common LFNSHL-related genes (WFS1, DIAPH1) and less common genes (TNC, EYA4), achieving a 44% genetic diagnosis rate. All genetically diagnosed patients had early adulthood-onset hearing loss except for one WFS1 variant case, and all exhibited progressive hearing loss. Our findings indicate that LFNSHL is predominantly inherited in an autosomal dominant manner. Further review showed that WFS1 mutations typically cause childhood-onset LFNSHL, while DIAPH1 and EYA4 mutations result in adulthood-onset LFNSHL; interestingly, WFS1 mutations generally progress to moderate hearing loss, milder than DIAPH1, TNC, and EYA4 mutations. Additionally, tinnitus was more prevalent in patients with WFS1, DIAPH1, and EYA4 mutations than those with TNC mutations. Notably, hearing loss deteriorated at all frequencies, becoming markedly severe after age 50 for TNC and WFS1 mutations, and after age 40 for EYA4 mutations. Mutations in WFS1 were predominantly missense, with the p.Ser807 codon and the protein’s C-terminal intracytoplasmic domain identified as mutation hotspots. Comparative analysis revealed a higher incidence of bilateral symmetrical progressive LFNSHL in genetically diagnosed patients than those without. This study, the first to investigate LFNSHL genetics in a Chinese cohort, underscores the complex genetic landscape and phenotypic variability of LFNSHL, providing valuable insights for future diagnostic and therapeutic strategies.
         datePublished:2024-12-25T00:00:00Z
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      headline:Genetic analysis of patients with low-frequency non-syndromic hearing loss
      description:Low-frequency non-syndromic hearing loss (LFNSHL) is a rare auditory disorder affecting frequencies ≤ 2000 Hz. To elucidate its genetic basis, we conducted whole-exome sequencing on nine Chinese families (31 affected individuals) with LFNSHL. Four heterozygous pathogenic variants, including two novel variants, were identified in common LFNSHL-related genes (WFS1, DIAPH1) and less common genes (TNC, EYA4), achieving a 44% genetic diagnosis rate. All genetically diagnosed patients had early adulthood-onset hearing loss except for one WFS1 variant case, and all exhibited progressive hearing loss. Our findings indicate that LFNSHL is predominantly inherited in an autosomal dominant manner. Further review showed that WFS1 mutations typically cause childhood-onset LFNSHL, while DIAPH1 and EYA4 mutations result in adulthood-onset LFNSHL; interestingly, WFS1 mutations generally progress to moderate hearing loss, milder than DIAPH1, TNC, and EYA4 mutations. Additionally, tinnitus was more prevalent in patients with WFS1, DIAPH1, and EYA4 mutations than those with TNC mutations. Notably, hearing loss deteriorated at all frequencies, becoming markedly severe after age 50 for TNC and WFS1 mutations, and after age 40 for EYA4 mutations. Mutations in WFS1 were predominantly missense, with the p.Ser807 codon and the protein’s C-terminal intracytoplasmic domain identified as mutation hotspots. Comparative analysis revealed a higher incidence of bilateral symmetrical progressive LFNSHL in genetically diagnosed patients than those without. This study, the first to investigate LFNSHL genetics in a Chinese cohort, underscores the complex genetic landscape and phenotypic variability of LFNSHL, providing valuable insights for future diagnostic and therapeutic strategies.
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      dateModified:2024-12-25T00:00:00Z
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         Low-frequency non-syndromic hearing loss
          WFS1
          DIAPH1
          TNC
          EYA4
         Plant Genetics and Genomics
         Human Genetics
         Microbial Genetics and Genomics
         Animal Genetics and Genomics
         Biochemistry
         general
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