{"title":"A genetic investigation in five Chinese families with keratoconus.","authors":"Qinghong Lin, Xuejun Wang, Xiaoliao Peng, Tian Han, Ling Sun, Xiaoyu Zhang, Xingtao Zhou","doi":"10.7717/peerj.18037","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study investigated the genetic characteristics of five Chinese families with keratoconus (KC).</p><p><strong>Methods: </strong>In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (<i>n</i> = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for <i>in silico</i> predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients.</p><p><strong>Results: </strong>The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (<i>HOMER3</i>) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (<i>IGF1R</i>) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (<i>EML6</i>) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (<i>DOP1B</i>) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (<i>NBEAL2</i>) gene. These variations were predicted to be potentially pathogenic and associated with KC.</p><p><strong>Conclusion: </strong>Five novel variants in <i>HOMER3, IGF1R, EML6, DOP1B</i>, and <i>NBEAL2</i> genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376248/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PeerJ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7717/peerj.18037","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: This study investigated the genetic characteristics of five Chinese families with keratoconus (KC).
Methods: In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (n = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for in silico predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients.
Results: The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (HOMER3) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (IGF1R) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (EML6) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (DOP1B) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (NBEAL2) gene. These variations were predicted to be potentially pathogenic and associated with KC.
Conclusion: Five novel variants in HOMER3, IGF1R, EML6, DOP1B, and NBEAL2 genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.
期刊介绍：
PeerJ is an open access peer-reviewed scientific journal covering research in the biological and medical sciences. At PeerJ, authors take out a lifetime publication plan (for as little as $99) which allows them to publish articles in the journal for free, forever. PeerJ has 5 Nobel Prize Winners on the Board; they have won several industry and media awards; and they are widely recognized as being one of the most interesting recent developments in academic publishing.
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