title: Novel missense mutations in lipase H (LIPH) gene causing autosomal recessive hypotrichosis (LAH2).
abstract: BACKGROUND
  Autosomal recessive hypotrishosis (LAH2) is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. However, affected male individuals have normal beard hair. Mutations in lipase H (LIPH) gene, located on chromosome 3q26.33, have been shown to be responsible for LAH2 type of hypotrichosis.
  
  
  OBJECTIVE
  To search for pathogenic mutations in LIPH gene at LAH2 locus in Pakistani families demonstrating autosomal recessive hypotrichosis.
  
  
  METHODS
  In the present study we have ascertained two large unrelated consanguineous Pakistani families (A and B) inherited autosomal recessive form of hypotrichosis. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene at LAH2 locus on chromosome 3q26.33. These families were then subjected to direct sequencing of the LIPH gene.
  
  
  RESULTS
  Sequence analysis of the LIPH gene revealed two novel missense mutations (c.2T>C; p.M1T and c.322T>C; p.W108R) in the two families.
  
  
  CONCLUSIONS
  The mutations reported here are the first missense mutations identified in the LIPH gene, which extend the body of evidences implicating the LIPH gene in the pathogenesis of human hereditary hair loss.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Gul
authors.initials: G
authors.lastname: Naz
authors.forename: Bushra
authors.initials: B
authors.lastname: Khan
authors.forename: Ghazanfar
authors.initials: G
authors.lastname: Ali
authors.forename: Zahid
authors.initials: Z
authors.lastname: Azeem
authors.forename: Abdul
authors.initials: A
authors.lastname: Wali
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics* / Q000473:pathology; D008049:Lipase / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: C504173:LIPC protein, human; D008049:Lipase