title: A novel missense mutation in MSX1 underlies autosomal recessive oligodontia with associated dental anomalies in Pakistani families.
abstract: Tooth agenesis constitutes the most common anomaly of dental development in humans. In the majority of familial cases of hypodontia alone or in association with other anomalies, the mode of inheritance is autosomal dominant. In the present study, we have identified two distantly related consanguineous Pakistani kindreds with an autosomal recessive form of oligodontia with associated dental anomalies. Locus in this case has been mapped on chromosome 4p16.1-p16.3. The maximum two-point LOD score of 2.85 (theta=0.0) was obtained at markers D4S2925 and D4S2285. A maximum multipoint LOD score exceeding 4 was obtained at the same markers. Recombination events observed in affected individuals localized the disease locus between markers D4S412 and D4S2935, spanning a 9.24-cM region on chromosome 4p16.1-p16.3. Sequence analysis of candidate gene MSX1 revealed a novel recessive missense mutation resulting in substitution of alanine to threonine amino acid (p. A219T), located in the MSX1 homeodomain, which is important for DNA binding and protein-protein interaction. The mutation, p. A219T, is the first recessive mutation identified in MSX1.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad S
authors.initials: MS
authors.lastname: Chishti
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Dost
authors.initials: D
authors.lastname: Muhammad
authors.affiliation: Department of Oral and Maxillofacial Surgery, Karachi Medical Dental College and Abbasi Shaheed Hospital, Karachi, Pakistan.
authors.forename: Mahmud
authors.initials: M
authors.lastname: Haider
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. wahmad@qau.edu.pk.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000848:Anodontia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005190:Family; D005808:Genes, Recessive; D006801:Humans; D008126:Lod Score; D051957:MSX1 Transcription Factor / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D011859:Radiography; D014071:Tooth Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human