title: A novel missense mutation in the EDA gene associated with X-linked recessive isolated hypodontia.
abstract: Isolated hypodontia, or congenital absence of one to six permanent teeth (OMIM 300606), is a common condition that affects about 20% of individuals worldwide. We identified two extended Pakistani pedigrees segregating X-linked hypodontia with variable expressivity. Affected males show no other associated anomalies, and obligate carrier females have normal dentition. We analyzed the families with polymorphic markers in the ectodysplasin A (EDA) gene region and obtained significant linkage to the phenotype in each pedigree (Z(max) 3.29 and 2.65, respectively, at theta = 0.00). Sequence analysis of the coding regions of EDA revealed a novel missense mutation c.1091T>C resulting in a methionine to threonine substitution (p.M364T) in the tumor necrosis factor (TNF) homology domain. Met364 is a highly conserved residue located on the outer surface of the EDA protein. From our findings, we suggest that the mutation disturbs but does not destroy the EDA structure, resulting in the partial and unusually mild ED phenotype restricted to hypodontia.
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
authors.affiliation: Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University and University Hospital, 751 85, Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Schuster
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Aslam
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Tariq
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Ilyas
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Amjad
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University and University Hospital, 751 85, Uppsala, Sweden.
authors.forename: Miriam
authors.initials: M
authors.lastname: Entesarian
authors.affiliation: Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University and University Hospital, 751 85, Uppsala, Sweden. niklas.dahl@genpat.uu.se.
authors.forename: Niklas
authors.initials: N
authors.lastname: Dahl
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors.forename: Shahid Mahmood
authors.initials: SM
authors.lastname: Baig
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000848:Anodontia / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D053331:Ectodysplasins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017510:Protein Folding; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins