title: Two novel mutations in the gene EDAR causing autosomal recessive hypohidrotic ectodermal dysplasia.
abstract: BACKGROUND
  Hypohidrotic ectodermal dysplasia (HED) is a human heritable disorder characterized by sparse hair, reduced ability to sweat and hypodontia. The HED exhibits X-linked, autosomal recessive and autosomal dominant mode of inheritance. Mutations in four genes including EDA, EDAR, EDARADD, and WNT10A are known to cause hypohidrotic and anhidrotic ectodermal dysplasia.
  
  
  METHODS
  Genotyping of both affected and normal individuals of two consanguineous Pakistani families (A, B), showing autosomal recessive HED, was carried out using microsatellite markers linked to EDAR gene on chromosome 2q11-q13. To screen for mutations in the gene EDAR, all of its exons and splice junction were amplified and sequenced directly, using an automated DNA sequencer.
  
  
  RESULTS
  Genotyping using microsatellite markers analysis showed linkage of the two families to gene EDAR on chromosome 2q11-2q13. Subsequently, screening of all the 12 exons and splice junctions of gene EDAR revealed a novel missense mutation (c.1163T>C; p.Ile388Thr) in family A and a novel insertion mutation (c.1014insA; p.V339SfsX6) in family B.
  
  
  CONCLUSIONS
  Our findings extend the body of evidence supporting the role of EDAR signaling pathway as a powerful regulator of development of ectodermal appendages.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: S K
authors.initials: SK
authors.lastname: Naqvi
authors.forename: N
authors.initials: N
authors.lastname: Wasif
authors.forename: H
authors.initials: H
authors.lastname: Javaid
authors.forename: W
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000225:Adenine; D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003241:Consanguinity; D003596:Cytosine; D053360:Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive / Q000235:genetics*; D053339:Edar Receptor / Q000235:genetics*; D005091:Exons / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D060005:Genotyping Techniques; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010154:Pakistan; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics; D017422:Sequence Analysis, DNA; D013912:Threonine / Q000235:genetics; D013941:Thymine; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: C506008:EDAR protein, human; D053339:Edar Receptor; D022821:RNA Splice Sites; D007532:Isoleucine; D013912:Threonine; D003596:Cytosine; D014633:Valine; D000225:Adenine; D013941:Thymine