title: Mutations in the LPAR6 and LIPH genes underlie autosomal recessive hypotrichosis/woolly hair in 17 consanguineous families from Pakistan.
abstract: BACKGROUND
  Autosomal recessive hypotrichosis/woolly hair is a rare genetic hair loss disorder characterized by sparse scalp hair/woolly hair, sparse to absent eyebrows and eyelashes, sparse axillary and body hair in affected individuals. This form of hair loss results from mutations in either LPAR6 or LIPH gene.
  
  
  OBJECTIVE
  To identify mutations in LPAR6 and LIPH genes in 17 consanguineous Pakistani families showing features of hypotrichosis/woolly hair.
  
  
  METHODS
  Genotyping in 17 families was carried out using polymorphic microsatellite markers linked to genes causing autosomal recessive hypotrichosis/woolly hair phenotype. To screen for mutations in LPAR6 and LIPH genes, all of their exons and splice junction sites were amplified by PCR and sequenced using an automated DNA sequencer.
  
  
  RESULTS
  Genotyping with polymorphic microsatellite markers showed linkage in eight families to LPAR6 and in nine families to LIPH gene. Sequence analysis revealed four recurrent mutations (p.Phe24HisfsX28; p.Asp63Val; p.Gly146Arg; p.Ile188Phe) in LPAR6 and two recurrent mutations (p.Trp108Arg; p.Ile220ArgfsX29) in LIPH gene. Comparison of the haplotypes generated by typing LPAR6 and LIPH genes linked microsatellite markers in different families suggested common founder natures of the two mutations (c.66_69insCATG and c.659_660delTA).
  
  
  CONCLUSIONS
  Mutations identified in the present study extend the body of evidence implicating LPAR6 and LIPH genes in pathogenesis of human hereditary hair loss.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: R
authors.initials: R
authors.lastname: Habib
authors.forename: H
authors.initials: H
authors.lastname: Mir
authors.lastname: Umm-e-Kalsoom
authors.forename: G
authors.initials: G
authors.lastname: Naz
authors.forename: M
authors.initials: M
authors.lastname: Ayub
authors.forename: S
authors.initials: S
authors.lastname: Shafique
authors.forename: T
authors.initials: T
authors.lastname: Yamin
authors.forename: N
authors.initials: N
authors.lastname: Ali
authors.forename: S
authors.initials: S
authors.lastname: Basit
authors.forename: N
authors.initials: N
authors.lastname: Wasif
authors.forename: S
authors.initials: S
authors.lastname: Kamran-Ul-Hassan Naqvi
authors.forename: G
authors.initials: G
authors.lastname: Ali
authors.forename: A
authors.initials: A
authors.lastname: Wali
authors.forename: M
authors.initials: M
authors.lastname: Ansar
authors.forename: W
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000328:Adult; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006201:Hair Diseases / Q000151:congenital* / Q000235:genetics; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics* / Q000473:pathology; D008049:Lipase / Q000235:genetics*; D008297:Male; D009154:Mutation; D010154:Pakistan; D010375:Pedigree; D010641:Phenotype; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*
chemical_list: C504173:LIPC protein, human; C545560:LPAR6 protein, human; D049368:Receptors, Lysophosphatidic Acid; D008049:Lipase