title: A novel homozygous PTH1R variant identified through whole-exome sequencing further expands the clinical spectrum of primary failure of tooth eruption in a consanguineous Saudi family.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Musharraf
authors.initials: M
authors.lastname: Jelani
authors.affiliation: Department of Biology and Institute of Basic Sciences, Sungshin Women's University, Seoul, Republic of Korea, Republic of Korea.
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Hussein Sheikh Ali
authors.initials: HS
authors.lastname: Mohamoud
authors.affiliation: Oral and Maxillofacial Prosthodontics Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Rayan
authors.initials: R
authors.lastname: Al-Rehaili
authors.affiliation: Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mona Mohammad
authors.initials: MM
authors.lastname: Almramhi
authors.affiliation: Department of Dermatology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
authors.forename: Rehab
authors.initials: R
authors.lastname: Serafi
authors.affiliation: Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; BGI-Shenzhen, Shenzhen, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Jumana Yousuf
authors.initials: JY
authors.lastname: Al-Aama
authors.affiliation: Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naeem
authors.affiliation: Oral and Maxillofacial Prosthodontics Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: yalkhiary@kau.edu.sa.
authors.forename: Yaser Mohammad
authors.initials: YM
authors.lastname: Alkhiary
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D003241:Consanguinity; D059472:Exome; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics*; D012529:Saudi Arabia; D014071:Tooth Abnormalities / Q000235:genetics*; D014078:Tooth Eruption / Q000235:genetics*; D055815:Young Adult
chemical_list: C473449:PTH1R protein, human; D044168:Receptor, Parathyroid Hormone, Type 1
keywords: Autosomal recessive; Consanguineous; Homozygous mutation; PTH1R; Primary failure of tooth eruption; Saudi Arabia