Medical Journal of the Islamic Republic Of Iran

en Genetic Characterization of Joubert Syndrome with COACH Features and in Silico Prediction of TMEM67 Gene Variants Based on Iranome Database Medical Genetics Medical Genetics Original Research Original Research     Background: Joubert syndrome (JS) is an uncommon genetic condition presenting with diverse clinical manifestations involving the nervous system, liver, and eyes. A specific form of JS, known as cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis (COACH) syndrome, is primarily associated with variants in the TMEM67 gene. This study aimed to identify the causative genetic variant in a patient with JS exhibiting the COACH phenotype and to investigate the spectrum and potential founder effects of TMEM67 gene variants within the Iranian population using the Iranome database    Methods: This study reports an 8-year-old girl with a family history of developmental delay who shows clinical features typical of JS with the COACH phenotype. To verify the disease-causing nature of the genetic variant, whole exome sequencing along with in silico analysis was conducted. The variant's conservation across species highlighted its functional significance, and a co-segregation study confirmed its inheritance pattern. Moreover, we collected all TMEM67 gene variants identified in the Iranome project.    Results: Our investigation revealed a homozygous missense variant in TMEM67 (c.725A>G; p.Asn242Ser) in the affected individual. Collective evidence from the Iranome database and previous studies demonstrates that this is a founder variant (c.725A>G) in the Iranian population.    Conclusion: This study highlights the intricate nature of JS and its genetic foundations, emphasizing the significance of founder variants in specific populations and the potential of national databases to enhance the precision of genetic diagnoses.   Joubert Syndrome, TMEM67, Whole exome sequencing, Iranian population 481 487 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-9645-1&slc_lang=en&sid=1 Seyyed Saleh Hashemi salehhashemi1995@gmail.com 200319475328460098105 200319475328460098105 No Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Amir Beigi Habibabadi beigiam@yahoo.com 200319475328460098106 0009-0009-9205-4543 No Department of Neurosciences, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Vahid Tayebi-khorrami vahidtayebi.kh@gmail.com 200319475328460098107 0009-0002-1031-7426 No Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Pegah Haidari pegah.haidari82@gmail.com 200319475328460098108 0009-0005-0317-2769 No Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran Saeed Esmaeili Dizghandi telomerase90@gmail.com 200319475328460098109 0009-0000-4215-8226 No Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran Samaneh Zafarabadi samane.zafarabadii@gmail.com 200319475328460098110 0009-0007-3306-9492 No Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran Shahram Salari shahramsalari1402@gmail.com 200319475328460098111 0009-0002-6114-7703 No Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mahdia Sayed mahdiasayed125@gmail.com 200319475328460098112 0009-0001-7042-0356 No Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran Ramin Raoufinia r.raoofi69@gmail.com 200319475328460098113 0009-0002-6162-8446 No Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mehdi Hassani hasani.mehdi2017@gmail.com 200319475328460098114 200319475328460098114 No Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Hamed Afarande afarande1379@gmail.com 200319475328460098115 0009-0007-6201-9574 No 1. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mir Salar Kahaei salarkahaei1372@gmail.com 200319475328460098116 200319475328460098116 No Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Amin Tadayoni Nia amintadayoni1@gmail.com 200319475328460098117 0009-0000-2302-5065 No Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Ali Arabnezhad aliarabnezhad238@gmail.com 200319475328460098118 0009-0001-7640-0858 No Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Setayesh Zamanpour Setayesh7221@gmail.com 200319475328460098119 200319475328460098119 No Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran Karim Naghipour Kojur NaghipourK4011@mums.ac.ir 200319475328460098120 200319475328460098120 Yes Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran