title: A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family.
abstract: Pure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and dominant inheritance fashion of PHNED occurs. In literature, to date, five different forms of PHNED have been reported at molecular level, having three genes known and two loci with no gene yet.
  
  
  
  In this study, a four generations consanguineous family of Pakistani origin with autosomal recessive PHNED was investigated. Affected members exhibited PHNED phenotypes with involvement of complete hair loss and nail dysplasia. To screen for mutation in the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries were sequenced. The 3D models of normal and mutated HOXC13 were predicted by using homology modeling.
  
  
  
  Through investigating the family to known loci, the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C; p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of the family. Due to mutation, loss of hydrogen bonding and difference in potential energy occurs, which may resulting in alteration of protein function.
  
  
  
  This is the first mutation reported in homeodomain, while 5thmutation reported in HOXC13 gene causing PHNED.
authors.affiliation: Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, 26000, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Anwar Kamal
authors.initials: AK
authors.lastname: Khan
authors.affiliation: Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, 26000, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Noor
authors.initials: N
authors.lastname: Muhammad
authors.affiliation: Department of Bioinformatics, Khushal Khan Khattak University, Karak, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, 26000, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Sher Alam
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Khadim
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Nasir
authors.affiliation: Gomal Centre of Biochemistry & Biotechnology, Gomal University, D.I.Khan, Pakistan.
authors.forename: Muzammil Ahmad
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, 26000, Khyber Pakhtunkhwa, Pakistan. saadkhanwazir@gmail.com.
authors.forename: Saadullah
authors.initials: S
authors.lastname: Khan
mesh_terms: D000328:Adult; D001665:Binding Sites; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D010154:Pakistan; D010641:Phenotype
chemical_list: C410305:HOXC13 protein, human; D018398:Homeodomain Proteins
keywords: HOXC13; Mutation; PHNED; Pakistani family