Research Article| Volume 54, ISSUE 1, P12-16, April 2009

Novel missense mutations in lipase H (LIPH) gene causing autosomal recessive hypotrichosis (LAH2)



      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.


      To search for pathogenic mutations in LIPH gene at LAH2 locus in Pakistani families demonstrating autosomal recessive hypotrichosis.


      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.


      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.


      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.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Dermatological Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Rafique M.A.
        • Ansar M.
        • Jamal S.M.
        • Malik S.
        • Sohail M.
        • Faiyaz-Ul-Haque M.
        • et al.
        A locus for hereditary hypotrichosis localized to human chromosome 18q21.1.
        Eur J Hum Genet. 2003; 11: 623-628
        • Aslam M.
        • Chahrour M.H.
        • Razzaq A.
        • Haque S.
        • Yan K.
        • Leal S.M.
        • et al.
        A novel locus for autosomal recessive form of hypotrichosis maps to chromosome 3q26.33–q27. 3.
        J Med Genet. 2004; 41: 849-852
        • Wali A.
        • Chishti M.S.
        • Ayub M.
        • Yasinzai M.
        • Kafaitullah
        • Ali G.
        • et al.
        Localization of a novel autosomal recessive hypotrichosis locus (LAH3) to chromosome 13q14.11–q21.32.
        Clin Genet. 2007; 72: 23-29
        • Kljuic A.
        • Bazzi H.
        • Sundberg J.P.
        • Martinez-Mir A.
        • O'Shaughnessy R.
        • Mahoney M.G.
        • et al.
        Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris.
        Cell. 2003; 113: 249-260
        • Rafiq M.A.
        • Ansar M.
        • Pham T.
        • Amin-ud-Din M.
        • Anwar M.
        • Haque S.
        • et al.
        Localization of a novel locus for hereditary nail dysplasia to chromosome 17q25.1–17q25.3.
        Clin Genet. 2004; 66: 73-78
        • Kazantseva A.
        • Goltsov A.
        • Zinchenko R.
        • Grigorenko A.P.
        • Abrukova A.V.
        • Moliaka Y.K.
        • et al.
        Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH.
        Science. 2006; 314: 982-985
        • Ali G.
        • Chishti M.S.
        • Raza S.I.
        • John P.
        • Ahmad W.
        A mutation in the lipase H (LIPH) gene underlie autosomal recessive hypotrichosis.
        Hum Genet. 2007; 121: 319-325
        • Jelani M.
        • Wasif N.
        • Ali G.
        • Chishti M.
        • Ahmad W.
        A novel deletion mutation in LIPH gene causes autosomal recessive hypotrichosis (LAH2).
        Clin Genet. 2008; 74: 184-188
        • Naqvi S.K.H.
        • Raza S.I.
        • Naveed A.K.
        • John P.
        • Ahmad W.
        A novel deletion mutation in the phospholipase H (LIPH) gene in a consanguineous Pakistani family with autosomal recessive hypotrichosis (LAH2).
        Br J Dermatol. 2009; 160: 194-196
        • Pasternack S.M.
        • von Kügelgen I.
        • Aboud K.A.
        • Lee Y.A.
        • Rüschendorf F.
        • Voss K.
        • et al.
        G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth.
        Nat Genet. 2008; 40: 329-334
        • Azeem Z.
        • Jelani M.
        • Naz G.
        • Tariq M.
        • Wasif N.
        • Kamran-Ul-Hassan Naqvi S.
        • et al.
        Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3).
        Hum Genet. 2008; 123: 515-519
        • Sonoda H.
        • Aoki J.
        • Hiramatsu T.
        • Ishida M.
        • Bandoh K.
        • Nagai Y.
        • et al.
        A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid.
        J Biol Chem. 2002; 277: 34254-34263
        • Sambrook J.
        • Fritsch E.F.
        • Maniatis T.
        Molecular cloning: a laboratory manual.
        2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY1989
        • Shimomura Y.
        • Wajid M.
        • Ishii Y.
        • Shapiro L.
        • Petukhova L.
        • Gordon D.
        • et al.
        Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair.
        Nat Genet. 2008; 40: 335-339
        • Ahmad W.
        • Faiyaz ul Haque M.
        • Brancolini V.
        • Tsou H.C.
        • ul Haque S.
        • Lam H.
        • et al.
        Alopecia universalis associated with a mutation in the human hairless gene.
        Science. 1998; 279: 720-724
        • Cichon S.
        • Anker M.
        • Vogt I.R.
        • Rohleder H.
        • Pützstück M.
        • Hillmer A.
        • et al.
        Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia.
        Hum Mol Genet. 1998; 7: 1671-1679
        • John P.
        • Tariq M.
        • Arshad Rafiq M.
        • Amin-Ud-Din M.
        • Muhammad D.
        • Waheed I.
        • et al.
        Recurrent intragenic deletion mutation in desmoglein 4 gene underlies autosomal recessive hypotrichosis in two Pakistani families of Balochi and Sindhi origins.
        Arch Dermatol Res. 2006; 298: 135-137
        • Yip L.
        • Horev L.
        • Sinclair R.
        • Zlotogorski A.
        Atrichia with papular lesions: a report of three novel human hairless gene mutations and a revision of diagnostic criteria.
        Acta Derm Venereol. 2008; 88: 346-349