{"title":"甲状旁腺激素1的一种新的杂合错义变异与髋关节发育不良的发生有关。","authors":"Dan Yang, Zaiwei Zhou, Shiqi Wang, Hao Ying, Sun Wang, Qichao Ma, Jing Wu, Qin Jiao, Lingyan Fan, Mengjie Chen, Yichen Wang, Lihua Zhao","doi":"10.1089/gtmb.2022.0078","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Developmental dysplasia of the hip (DDH) is one of the most common diseases in the pediatric orthopedics, with an incidence of 1-5%. Genetic factors are the bases of the pathogenesis of DDH, but the pathogenic variants and pathogenesis of DDH are still unknown. There are no key accurate diagnostic or prognostic molecular markers for DDH. The purpose of our study was to screen for genetic variant associated with DDH and explore its pathogenesis. <b><i>Materials and Methods:</i></b> The genetic variation of DDH was tested by variant NGS-based exome analyses, verified by the Sanger sequencing. <b><i>Results:</i></b> A four-generation family in which DDH was present in three generations was recruited. A novel heterozygous missense variant c.629C>T (p.(Ala210Val)) in exon 7/8 of the parathyroid hormone 1 receptor (<i>PTH1R</i>) gene was identified through screening of two affected and one unaffected family members. The candidate variant was validated in all available family members with all three affected members being positive for the <i>PTH1R</i> variant. <b><i>Conclusion:</i></b> Our results are highly supportive of <i>PTH1R</i> as a novel candidate gene for DDH and demonstrated that the combination of pedigree information and next-generation sequencing is an effective method for identifying pathogenic variants associated with DDH.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Novel Heterozygous Missense Variant in <i>Parathyroid Hormone 1</i> is Related to the Occurrence of Developmental Dysplasia of the Hip.\",\"authors\":\"Dan Yang, Zaiwei Zhou, Shiqi Wang, Hao Ying, Sun Wang, Qichao Ma, Jing Wu, Qin Jiao, Lingyan Fan, Mengjie Chen, Yichen Wang, Lihua Zhao\",\"doi\":\"10.1089/gtmb.2022.0078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Introduction:</i></b> Developmental dysplasia of the hip (DDH) is one of the most common diseases in the pediatric orthopedics, with an incidence of 1-5%. Genetic factors are the bases of the pathogenesis of DDH, but the pathogenic variants and pathogenesis of DDH are still unknown. There are no key accurate diagnostic or prognostic molecular markers for DDH. The purpose of our study was to screen for genetic variant associated with DDH and explore its pathogenesis. <b><i>Materials and Methods:</i></b> The genetic variation of DDH was tested by variant NGS-based exome analyses, verified by the Sanger sequencing. <b><i>Results:</i></b> A four-generation family in which DDH was present in three generations was recruited. A novel heterozygous missense variant c.629C>T (p.(Ala210Val)) in exon 7/8 of the parathyroid hormone 1 receptor (<i>PTH1R</i>) gene was identified through screening of two affected and one unaffected family members. The candidate variant was validated in all available family members with all three affected members being positive for the <i>PTH1R</i> variant. <b><i>Conclusion:</i></b> Our results are highly supportive of <i>PTH1R</i> as a novel candidate gene for DDH and demonstrated that the combination of pedigree information and next-generation sequencing is an effective method for identifying pathogenic variants associated with DDH.</p>\",\"PeriodicalId\":12603,\"journal\":{\"name\":\"Genetic testing and molecular biomarkers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetic testing and molecular biomarkers\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/gtmb.2022.0078\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic testing and molecular biomarkers","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/gtmb.2022.0078","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
髋关节发育不良(Developmental dysplasia of the hip, DDH)是儿科骨科最常见的疾病之一,发病率为1-5%。遗传因素是DDH发病的基础,但DDH的致病变异和发病机制尚不清楚。DDH没有关键的准确诊断或预后分子标记物。我们的研究目的是筛选与DDH相关的遗传变异并探讨其发病机制。材料和方法:采用基于变异ngs的外显子组分析检测DDH的遗传变异,并通过Sanger测序进行验证。结果:招募了一个四代家族,其中三代都有DDH。通过筛选两名甲状旁腺激素1受体(PTH1R)家族成员,在PTH1R基因外显子7/8中发现了一种新的杂合错义变异c.629C>T (p.(Ala210Val))。候选变异在所有可用的家庭成员中得到验证,所有三个受影响的成员都是PTH1R变异阳性。结论:我们的研究结果高度支持PTH1R作为DDH的新候选基因,并证明将家系信息与下一代测序相结合是鉴定DDH相关致病变异的有效方法。
A Novel Heterozygous Missense Variant in Parathyroid Hormone 1 is Related to the Occurrence of Developmental Dysplasia of the Hip.
Introduction: Developmental dysplasia of the hip (DDH) is one of the most common diseases in the pediatric orthopedics, with an incidence of 1-5%. Genetic factors are the bases of the pathogenesis of DDH, but the pathogenic variants and pathogenesis of DDH are still unknown. There are no key accurate diagnostic or prognostic molecular markers for DDH. The purpose of our study was to screen for genetic variant associated with DDH and explore its pathogenesis. Materials and Methods: The genetic variation of DDH was tested by variant NGS-based exome analyses, verified by the Sanger sequencing. Results: A four-generation family in which DDH was present in three generations was recruited. A novel heterozygous missense variant c.629C>T (p.(Ala210Val)) in exon 7/8 of the parathyroid hormone 1 receptor (PTH1R) gene was identified through screening of two affected and one unaffected family members. The candidate variant was validated in all available family members with all three affected members being positive for the PTH1R variant. Conclusion: Our results are highly supportive of PTH1R as a novel candidate gene for DDH and demonstrated that the combination of pedigree information and next-generation sequencing is an effective method for identifying pathogenic variants associated with DDH.
期刊介绍:
Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results.
Genetic Testing and Molecular Biomarkers coverage includes:
-Diagnosis across the life span-
Risk assessment-
Carrier detection in individuals, couples, and populations-
Novel methods and new instrumentation for genetic testing-
Results of molecular, biochemical, and cytogenetic testing-
Genetic counseling