title: Mutations in MSX1, PAX9 and MMP20 genes in Saudi Arabian patients with tooth agenesis.
abstract: Tooth agenesis in human being is the most common congenital anomaly associated with dental development. Mutations in many genes such as MSH homeobox 1 (MSX1), paired box gene 9 (PAX9), ectodysplasin A (EDA) and EDA receptor (EDAR) have been associated with familial form of this condition. However, in large majority of patients, genetic cause could not be identified. The primary aim of present study was to identify the causative mutation(s) in these genes in Saudi Arabian families diagnosed with non-syndromic form of disease. Direct sequencing of coding regions, including exon-intron boundaries of these genes was carried out. All identified nucleotide variations were also tested to exclude possibility of being rare polymorphisms. The sequence analysis of exons and exon-intronic regions of these genes revealed five new mutations that include four in MSX1, one in PAX9 and one single nucleotide polymorphism (SNP) in majority of the patients in MMP20. One novel mutation in exon 1 of MSX1 gene (5354C > G; A40G) was found in three patients. In addition, another novel mutation was detected in two patients in exon 3 (PAX9) as g.10672A > T which changes asparagine to isoleucine at position 40. These mutations were not found in any of the control subjects. A single SNP in MMP20 genes (g.5066A > C) that changes lysine to threonine at position 18 was found in 10% controls as well. Our results for the first time demonstrates that mutations in MSX1 gene might play an important role in hypodontia cases involving pre-molars and is a risk factor for this ethnic population mainly of Arabs and is first report linking these mutations with tooth agenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia. Electronic address: dr.shahid90@yahoo.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Division of Endodontics, Department of Restorative Dental Science, Dental Caries Research Chair, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hanan A
authors.initials: HA
authors.lastname: Balto
authors.affiliation: Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nouf
authors.initials: N
authors.lastname: Al-Hammad
authors.affiliation: Department of Biotechnology, Punjab University Chandigarh, India.
authors.forename: S
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hesham Saleh
authors.initials: HS
authors.lastname: Khalil
authors.affiliation: Department of Pathology/Microbiology, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ali Mohammed
authors.initials: AM
authors.lastname: Somily
authors.affiliation: Department of Laboratories, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nasr Abdul-Aziz
authors.initials: NA
authors.lastname: Sinjilawi
authors.affiliation: Department of Family Medicine, College of Medicine, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.
authors.forename: Sameer
authors.initials: S
authors.lastname: Al-Ghamdi
authors.affiliation: Department of Pathology, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Faiyaz-Ul-Haque
authors.affiliation: Food and Nutrition, Commonwealth Scientific and Industrial Research Organization (CSIRO), Gate 13, Kintore Avenue, Adelaide, 5000 Australia. Electronic address: varinderpal.dhillon@csiro.au.
authors.forename: Varinderpal S
authors.initials: VS
authors.lastname: Dhillon
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000848:Anodontia / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D023061:Gene Order; D005838:Genotype; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics*; D008297:Male; D053519:Matrix Metalloproteinase 20 / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D051764:PAX9 Transcription Factor / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia; D055815:Young Adult
chemical_list: D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D053519:Matrix Metalloproteinase 20
keywords: Agenesis; Hypodontia; Mutations; Oligodontia; Sequencing; Tooth development