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. Objectives 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. Conclusion 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.