title: Recurrent mutations in functionally-related EDA and EDAR genes underlie X-linked isolated hypodontia and autosomal recessive hypohidrotic ectodermal dysplasia.
abstract: Mutations in three functionally related genes EDA, EDAR and EDARDD have been reported to cause hypohidrotic ectodermal dysplasia (HED), which is characterized by sparse hair, reduced ability to sweat, and hypodontia. In few cases mutations in the EDA gene have been found to result in X-linked recessive isolated hypodontia. In the study, presented here, we have ascertained two large Pakistani families (A and B) with autosomal recessive form of hypohidrotic ectodermal dysplasia and X-linked recessive isolated hypodontia. Genetic mapping showed linkage of family A to EDAR gene on chromosome 2q11-q13 and family B to EDA gene on chromosome Xq12-q13.1. Subsequently, DNA sequencing of the coding regions of EDAR and EDA genes revealed previously described mutations. Sequence analysis identified a four base-pair splice-junction deletion mutation (c.718_721delAAAG) in EDAR gene in family A and a missense mutation (c.T1091C; p.M364T) in EDA gene in family B. Recurrence of mutations in EDAR and EDA genes in unrelated families is evocative of the dispersion of ancestral chromosome in different locality groups through common ancestors.
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors: Zahid
authors: Z
authors: Azeem
authors: Syed Kamran-Ul-Hassan
authors: SK
authors: Naqvi
authors: Muhammad
authors: M
authors: Ansar
authors: Abdul
authors: A
authors: Wali
authors: Abdul Khaliq
authors: AK
authors: Naveed
authors: Ghazanfar
authors: G
authors: Ali
authors: Muhammad Jawad
authors: MJ
authors: Hassan
authors: Muhammad
authors: M
authors: Tariq
authors: Sulman
authors: S
authors: Basit
authors: Wasim
authors: W
authors: Ahmad
mesh_terms: D000848:Anodontia / Q000235:genetics*; D053360:Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D053339:Edar Receptor / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D012008:Recurrence
chemical_list: C506018:EDA protein, human; C506008:EDAR protein, human; D053331:Ectodysplasins; D053339:Edar Receptor