Erfan Khorram, Omid Iravani, Mehdi Khorrami, Masoomeh Amini, Sara Jahanian, Mohammad Hossein Nilforoush, Seyyed Reza Mousavi, Mahsa Ehsanifard, Majid Kheirollahi
{"title":"非典型USH1D家族CDH23基因新双等位变异:文献综述及基因型-表型相关性研究","authors":"Erfan Khorram, Omid Iravani, Mehdi Khorrami, Masoomeh Amini, Sara Jahanian, Mohammad Hossein Nilforoush, Seyyed Reza Mousavi, Mahsa Ehsanifard, Majid Kheirollahi","doi":"10.1159/000529420","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients' manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established.</p><p><strong>Methods: </strong>Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2.</p><p><strong>Results: </strong>Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation.</p><p><strong>Conclusion: </strong>By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. Also, reviewing the literature shows that, contrary to previous claims, different genotypes occur in the CDH23 gene allelic disorders, and there is no clear-cut genotype-phenotype correlation.</p>","PeriodicalId":55432,"journal":{"name":"Audiology and Neuro-Otology","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation.\",\"authors\":\"Erfan Khorram, Omid Iravani, Mehdi Khorrami, Masoomeh Amini, Sara Jahanian, Mohammad Hossein Nilforoush, Seyyed Reza Mousavi, Mahsa Ehsanifard, Majid Kheirollahi\",\"doi\":\"10.1159/000529420\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients' manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established.</p><p><strong>Methods: </strong>Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2.</p><p><strong>Results: </strong>Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation.</p><p><strong>Conclusion: </strong>By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. 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A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation.
Introduction: Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients' manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established.
Methods: Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2.
Results: Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation.
Conclusion: By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. Also, reviewing the literature shows that, contrary to previous claims, different genotypes occur in the CDH23 gene allelic disorders, and there is no clear-cut genotype-phenotype correlation.
期刊介绍：
''Audiology and Neurotology'' provides a forum for the publication of the most-advanced and rigorous scientific research related to the basic science and clinical aspects of the auditory and vestibular system and diseases of the ear. This journal seeks submission of cutting edge research opening up new and innovative fields of study that may improve our understanding and treatment of patients with disorders of the auditory and vestibular systems, their central connections and their perception in the central nervous system. In addition to original papers the journal also offers invited review articles on current topics written by leading experts in the field. The journal is of primary importance for all scientists and practitioners interested in audiology, otology and neurotology, auditory neurosciences and related disciplines.
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