title: WNT10A coding variants and maxillary lateral incisor agenesis with associated dental anomalies.
abstract: Congenital maxillary lateral incisor agenesis (MLIA) is one of the most common subtypes of dental agenesis. Because little is known with regard to the aetiology of this anomaly, the aim of the study was to determine the contribution of nucleotide variants in wingless-type MMTV integration site family, member 10A (WNT10A), msh homeobox 1 (MSX1), and paired box 9 (PAX9) to the risk of MLIA in a Polish population. Coding regions of the selected genes were analysed by direct sequencing in a group of 20 individuals with unilateral and bilateral MLIA, associated or not with other dental anomalies. The frequencies of the identified nucleotide variants were assessed in an additional cohort of patients with isolated dental agenesis (n = 147) and in 178 controls. Mutation screening showed four non-synonymous substitutions located in the highly conserved coding sequence of WNT10A in five (25%) of the 20 patients. Analysis of genotyping results revealed that three of these variants--p.Arg113Cys, p.Phe228Ile, and the newly identified p.Arg171Leu--may represent aetiological mutations underlying MLIA with associated dental anomalies. No mutations that were potentially aetiologic were identified in MSX1 and PAX9. In conclusion, this is the first report implicating coding variants in the WNT10A gene in the aetiology of MLIA. These results will require further confirmation using larger-scale studies.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Adrianna
authors.initials: A
authors.lastname: Mostowska
authors.forename: Barbara
authors.initials: B
authors.lastname: Biedziak
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zadurska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Matuszewska-Trojan
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D000293:Adolescent; D000328:Adult; D000848:Anodontia / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D017124:Conserved Sequence / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007180:Incisor / Q000002:abnormalities*; D007532:Isoleucine / Q000235:genetics; D007930:Leucine / Q000235:genetics; D051957:MSX1 Transcription Factor / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics*; D051764:PAX9 Transcription Factor / Q000235:genetics; D010649:Phenylalanine / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D014071:Tooth Abnormalities / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; C484142:WNT10A protein, human; D051153:Wnt Proteins; D007532:Isoleucine; D010649:Phenylalanine; D001120:Arginine; D007930:Leucine; D003545:Cysteine
keywords: maxillary lateral incisor agenesis; msh homeobox 1 (MSX1); msh homeobox 1 (PAX9); mutation; wingless-type MMTV integration site family, member 10A (WNT10A)