title: Disease causing homozygous variants in the human hairless gene.
abstract: BACKGROUND
  Atrichia with papular lesions (APL) is a rare irreversible form of complete hair loss inherited in autosomal recessive manner. Hair loss is often followed by the appearance of multiple keratin-filled cysts or papules on exterior parts of the body. This phenotype results due to mutations in the human hairless gene (HR) mapped on chromosome 8p21.3. The present study was aimed to search for disease-causing sequence variants in the HR gene in five consanguineous families exhibiting features of APL.
  
  
  METHODS
  Linkage in five Pakistani lineal consanguineous families, displaying features of APL, was tested using microsatellite markers flanking the HR gene on chromosome 8p21.3. After constructing the haplotypes, variants in the gene HR were searched by dideoxy-chain termination sequencing.
  
  
  RESULTS
  Haplotype analysis established linkage in all five families to the HR gene located on chromosome 8p.21.3. Subsequently, sequencing HR identified a novel homozygous nonsense variant (c.2541G>A, p.Trp847*) in one and previously reported two pathogenic variants (p.Cys690*, p.Pro1157Arg) in the other four families.
  
  
  CONCLUSIONS
  Mutations identified extend the spectrum of mutations in the HR gene resulting in APL. Characterizing the clinical spectrum resulting from the disease-causing homozygous variants in the HR gene will direct clinical care of the family members.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Sabba
authors.initials: S
authors.lastname: Mehmood
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.|Department of Biotechnology & Genetic Engineering, Kohat University of Science & Technology (KUST), Kohat, Pakistan.
authors.forename: Abid
authors.initials: A
authors.lastname: Jan
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.|Army Medical College, National University of Science & Technology (NUST), Islamabad, Pakistan.
authors.forename: Syed Irfan
authors.initials: SI
authors.lastname: Raza
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Farooq
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Younus
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.lastname: Irfanullah
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Shamim
authors.initials: S
authors.lastname: Shahi
authors.affiliation: Institute of Biochemistry, University of Baluchistan, Quetta, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayub
authors.affiliation: Department of Biotechnology & Genetic Engineering, Kohat University of Science & Technology (KUST), Kohat, Pakistan.
authors.forename: Saadullah
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000505:Alopecia / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D003241:Consanguinity; D005260:Female; D018859:Hair Follicle / Q000002:abnormalities*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D012872:Skin Diseases, Vesiculobullous / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C490267:HR protein, human; D014157:Transcription Factors