Musharraf Jelani1, Changsoo Kang2, Hussein Sheikh Ali Mohamoud3, Rayan Al-Rehaili4, Mona Mohammad Almramhi5, Rehab Serafi6, Huanming Yang7, Jumana Yousuf Al-Aama8, Muhammad Naeem9, Yaser Mohammad Alkhiary10. 1. Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Medical Genetics and Molecular Biology Unit, Biochemistry Department, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. Electronic address: mjelani@kau.edu.sa. 2. Department of Biology and Institute of Basic Sciences, Sungshin Women's University, Seoul, Republic of Korea, Republic of Korea. 3. Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Human Genetics Research Centre, Division of Biomedical Sciences (BMS), St. George's University of London (SGUL), London SW17 0RE, United Kingdom, UK. 4. Oral and Maxillofacial Prosthodontics Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia. 5. Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. 6. Department of Dermatology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia. 7. Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; BGI-Shenzhen, Shenzhen, China. 8. Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. 9. Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan. 10. Oral and Maxillofacial Prosthodontics Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: yalkhiary@kau.edu.sa.
Abstract
OBJECTIVES: The present study aimed to identify the genetic cause of non-syndromic primary failure of tooth eruption in a five-generation consanguineous Saudi family using whole-exome sequencing (WES) analysis. DESIGN: The family pedigree and phenotype were obtained from patient medical records. WES of all four affected family members was performed using the 51 Mb SureSelect V4 library kit and then sequenced using the Illumina HiSeq2000 sequencing system. Sequence alignment, variant calling, and the annotation of single nucleotide polymorphisms and indels were performed using standard bioinformatics pipelines. The genotype of candidate variants was confirmed in all available family members by Sanger sequencing. RESULTS: Pedigree analysis suggested that the inheritance was autosomal recessive. WES of all affected individuals identified a novel homozygous variant in exon 8 of the parathyroid hormone 1 receptor gene (PTH1R) (NM_000316: c.611T>A: p.Val204Glu). CONCLUSION: To the best of our knowledge, this is the first report of primary failure of eruption caused by a homozygous mutation in PTH1R. Our findings prove the application of WES as an efficient molecular diagnostics tool for this rare phenotype and further broaden the clinical spectrum of PTH1R pathogenicity.
OBJECTIVES: The present study aimed to identify the genetic cause of non-syndromic primary failure of tooth eruption in a five-generation consanguineous Saudi family using whole-exome sequencing (WES) analysis. DESIGN: The family pedigree and phenotype were obtained from patient medical records. WES of all four affected family members was performed using the 51 Mb SureSelect V4 library kit and then sequenced using the Illumina HiSeq2000 sequencing system. Sequence alignment, variant calling, and the annotation of single nucleotide polymorphisms and indels were performed using standard bioinformatics pipelines. The genotype of candidate variants was confirmed in all available family members by Sanger sequencing. RESULTS: Pedigree analysis suggested that the inheritance was autosomal recessive. WES of all affected individuals identified a novel homozygous variant in exon 8 of the parathyroid hormone 1 receptor gene (PTH1R) (NM_000316: c.611T>A: p.Val204Glu). CONCLUSION: To the best of our knowledge, this is the first report of primary failure of eruption caused by a homozygous mutation in PTH1R. Our findings prove the application of WES as an efficient molecular diagnostics tool for this rare phenotype and further broaden the clinical spectrum of PTH1R pathogenicity.
Authors: Akira Takahashi; Mizuki Nagata; Aditi Gupta; Yuki Matsushita; Tetsutaro Yamaguchi; Koji Mizuhashi; Koutaro Maki; Antonio C Ruellas; Lucia S Cevidanes; Henry M Kronenberg; Noriaki Ono; Wanida Ono Journal: Proc Natl Acad Sci U S A Date: 2018-12-03 Impact factor: 11.205
Authors: Ali A Assiry; Alia M Albalawi; Muhammad S Zafar; Siraj D Khan; Anhar Ullah; Ahmed Almatrafi; Khushnooda Ramzan; Sulman Basit Journal: Sci Rep Date: 2019-11-11 Impact factor: 4.379