Mohammad Soudyab, Mohammad Shariati, Reza Jafarzadeh Esfehani, Neda Shalaei, Shabnam Vafadar, Vahid Nouri, Michael Zech, Julianne Winkelmann, Ali Shoeibi, Ariane Sadr-Nabavi
{"title":"近亲帕金森病家族和相关表型的全外显子组测序研究:12个新变体的报告","authors":"Mohammad Soudyab, Mohammad Shariati, Reza Jafarzadeh Esfehani, Neda Shalaei, Shabnam Vafadar, Vahid Nouri, Michael Zech, Julianne Winkelmann, Ali Shoeibi, Ariane Sadr-Nabavi","doi":"10.1007/s12031-022-02085-9","DOIUrl":null,"url":null,"abstract":"<div><p>Parkinson’s disease (PD) is a common progressive neurodegenerative disorder with motor and nonmotor symptoms. Recent studies demonstrate various susceptibility loci and candidate genes for familial forms of the disease. However, the genetic basis of the familial form of early-onset PD (EOPD) is not widely studied in the Iranian population. Therefore, the present study aimed to investigate the possible causative genetic variants responsible for developing EOPD among Iranian patients. Iranian patients with a clinical diagnosis of Parkinson’s disease were evaluated, and 12 consanguineous families with at least two affected individuals with early-onset PD (EOPD) were chosen to enroll in the present study. An expert neurologist group examined these families. Whole-exome sequencing (WES) was performed on PD patients, and the possible causative genetic variants related to the development of PD were reported. Exome sequencing (WES) was performed on every PD patient and revealed that patients had novel genetic variants in <i>PRKN</i>, <i>PARK7</i>, and <i>PINK1</i> genes. All the genetic variants were in homozygous status and none of these variants were previously reported in the literature. Moreover, these genetic variants were “pathogenic” based on bioinformatic studies and according to the American College of Medical Genetics (ACMG). The present research revealed some novel variants for EOPD among the Iranian population. Further functional studies are warranted to confirm the pathogenicity of these novel variants and establish their clinical application for the early diagnosis of EOPD.\n</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 12","pages":"2486 - 2496"},"PeriodicalIF":2.8000,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Whole-Exome Sequencing Study of Consanguineous Parkinson’s Disease Families and Related Phenotypes: Report of Twelve Novel Variants\",\"authors\":\"Mohammad Soudyab, Mohammad Shariati, Reza Jafarzadeh Esfehani, Neda Shalaei, Shabnam Vafadar, Vahid Nouri, Michael Zech, Julianne Winkelmann, Ali Shoeibi, Ariane Sadr-Nabavi\",\"doi\":\"10.1007/s12031-022-02085-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Parkinson’s disease (PD) is a common progressive neurodegenerative disorder with motor and nonmotor symptoms. Recent studies demonstrate various susceptibility loci and candidate genes for familial forms of the disease. However, the genetic basis of the familial form of early-onset PD (EOPD) is not widely studied in the Iranian population. Therefore, the present study aimed to investigate the possible causative genetic variants responsible for developing EOPD among Iranian patients. Iranian patients with a clinical diagnosis of Parkinson’s disease were evaluated, and 12 consanguineous families with at least two affected individuals with early-onset PD (EOPD) were chosen to enroll in the present study. An expert neurologist group examined these families. Whole-exome sequencing (WES) was performed on PD patients, and the possible causative genetic variants related to the development of PD were reported. Exome sequencing (WES) was performed on every PD patient and revealed that patients had novel genetic variants in <i>PRKN</i>, <i>PARK7</i>, and <i>PINK1</i> genes. All the genetic variants were in homozygous status and none of these variants were previously reported in the literature. Moreover, these genetic variants were “pathogenic” based on bioinformatic studies and according to the American College of Medical Genetics (ACMG). The present research revealed some novel variants for EOPD among the Iranian population. Further functional studies are warranted to confirm the pathogenicity of these novel variants and establish their clinical application for the early diagnosis of EOPD.\\n</p></div>\",\"PeriodicalId\":652,\"journal\":{\"name\":\"Journal of Molecular Neuroscience\",\"volume\":\"72 12\",\"pages\":\"2486 - 2496\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2022-12-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12031-022-02085-9\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12031-022-02085-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Whole-Exome Sequencing Study of Consanguineous Parkinson’s Disease Families and Related Phenotypes: Report of Twelve Novel Variants
Parkinson’s disease (PD) is a common progressive neurodegenerative disorder with motor and nonmotor symptoms. Recent studies demonstrate various susceptibility loci and candidate genes for familial forms of the disease. However, the genetic basis of the familial form of early-onset PD (EOPD) is not widely studied in the Iranian population. Therefore, the present study aimed to investigate the possible causative genetic variants responsible for developing EOPD among Iranian patients. Iranian patients with a clinical diagnosis of Parkinson’s disease were evaluated, and 12 consanguineous families with at least two affected individuals with early-onset PD (EOPD) were chosen to enroll in the present study. An expert neurologist group examined these families. Whole-exome sequencing (WES) was performed on PD patients, and the possible causative genetic variants related to the development of PD were reported. Exome sequencing (WES) was performed on every PD patient and revealed that patients had novel genetic variants in PRKN, PARK7, and PINK1 genes. All the genetic variants were in homozygous status and none of these variants were previously reported in the literature. Moreover, these genetic variants were “pathogenic” based on bioinformatic studies and according to the American College of Medical Genetics (ACMG). The present research revealed some novel variants for EOPD among the Iranian population. Further functional studies are warranted to confirm the pathogenicity of these novel variants and establish their clinical application for the early diagnosis of EOPD.
期刊介绍:
The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.