Abstract
Hereditary hypotrichosis is a rare autosomal recessive condition characterized clinically by alopecia. Three consanguineous kindreds with multiple affected individuals were ascertained from different regions of Pakistan. A novel hypotrichosis locus was mapped to a 5.5 cM region on chromosome 18q21.1. A maximum two-point LOD score of 5.25 was obtained at marker D18S36 (θ=0.0). Three genes each for desmoglein and desmocollin proteins are located in this region. The expression in epidermal desmosomes and their connection to the keratin intermediate filaments make these genes excellent candidates for recessive hypotrichosis.
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References
Ahmad W, Haque MF, Lam HM et al: Alopecia Universalis associated with a mutation in the human hairless gene. Science 1998; 279: 720–724.
Ahmad W, Invine A, Lam HM et al: A missense mutation in the zinc-finger domain of the human hairless gene underlies congenital atrichia in a family of irish travellers. Am J Hum Genet 1998; 63: 984–989.
Ahmad W, Zlotogorski A, Andrie A et al: Genomic organization of the human hairless gene and identification of a mutation underlying congenital atrichia in an Arab Palestinian family. Genomics 1999; 56: 141–148.
Cichon S, Anker M, Vogt IR 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.
Toribio J, Quinones PA : Hereditary hypotrichosis simplex of the scalp – evidence for autosomal dominant inheritance. Br J Dermatol 1974; 91: 687–696.
Betz RC, Lee YA, Bygum A et al: A gene for hypotrichosis simplex of the scalp maps to chromosome 6p21.3. Am J Hum Genet 2000; 66: 1979–1983.
Unna M : Ueber Hypotrichosis congenita hereditaria. Derm Wschr 1925; 81: 1167–1178.
Argenziano G, Sammarco E, Rossi A, Delfino M, Calvieri S : Marie Unna hereditary hypotrichosis. Eur J Dermatol 1999; 9: 278–280.
Sreekumar GP, Roberts JL, Wong C-Q, Stenn KS, Parimoo S : Marie Unna hereditary hypotrichosis gene maps to human chromosome 8p21 near hairless. J Invest Dermatol 2000; 114: 595–597.
Lefevre P, Rochat A, Bodemer C et al: Linkage of Marie Unna hypotrichosis locus to chromosome 8p21 and exclusion of 10 genes including the hairless gene by mutation analysis. Eur J Hum Genet 2000; 8: 273–279.
Baumer A, Belli S, Trueb RM, Schinzel A : An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32–p11.23 in an Italian family. Eur J Hum Genet 2000; 8: 443–448.
Winter H, Labreze C, Chapalain V et al: A variable monilethrix phenotype associated with a novel mutation, glu402lys, in the helix termination motif of the type II hair keratin hHb1. J Invest Dermatol 1998; 111: 169–172.
Segre JA, Nemhauser JL, Taylor BA, Nadeau JH, Lander ES : Positional cloning of the nude locus: genetic, physical, and transcription maps of the region and mutations in the mouse and rat. Genomics 1995; 28: 549–559.
Frank J, Pignata C, Panteleyev AA et al: Exposing the human nude phenotype. Nature 1999; 398: 473–474.
Netherton EW : A unique case of trichorrhexis nodosa: ‘bamboo hairs’. Arch Dermatol 1958; 78: 483–487.
Smith DL, Smith JG, Wong SW, de Shazo RD : Netherton's syndrome: a syndrome of elevated IgE and characteristic skin and hair findings. J Allergy Clin Immunol 1995; 95: 116–123.
Chavanas S, Garner C, Bodemer C et al: Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping. Am J Hum Genet 2000; 66: 914–921.
Schaffer AA : Fast linkage analysis computations for pedigrees with loops or unused alleles. Hum Hered 1996; 46: 226–235.
Nothen MM, Cichon S, Vogt IR et al: A gene for universal congenital alopecia maps to chromosome 8p21–22. Am J Hum Genet 1998; 62: 386–390.
Ho L, Williams MS, Spritz RA : A gene for autosomal dominant hypohidrotic ectodermal dysplasia (EDA3) maps to chromosome 2q11–q13. Am J Hum Genet 1998; 62: 1102–1106.
Suzuki K, Bustos T, Spritz RA : Linkage disequilibrium mapping of the gene for Margarita Island ectodermal dysplasia (ED4) to 11q23. Am J Hum Genet 1998; 63: 1102–1107.
Kibar Z, Kaloustian VMD, Brais B et al: The gene responsible for Cloustan Hydrotic ectodermal dysplasia maps to the peri-centromeric region of chromosome 13q. Hum Mol Genet 1996; 5: 543–547.
Healy E, Holmes SC, Belgaid CE et al: A gene for monilethrix is closely linked to the type II keratin gene cluster at 12q13. Hum Mol Genet 1995; 4: 2399–2402.
Krebsova A, Hamm H, Karl S et al: Assignment of the gene for a new hereditary nail disorder, isolated congenital nail dysplasia, to chromosome 17p13. J Invest Dermatol 1999; 115: 664–667.
Broman KW, Murray JC, Sheffield VC et al: Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet 1998; 63: 861–869.
Simrak D, Cowley CME, Buxton RS, Arnemann J : Tandem arrangement of the closely linked desmoglein genes on human chromosome 18. Genomics 1995; 25: 591–594.
King IA, Sullivan KH, Bennett RS, Buxton RS : The desmocollins of human foreskin epidermis: identification and chromosomal assignment of a third gene and expression patterns of the three isoforms. J Invest Dematol 1995; 105: 314–321.
Townes TM, Behringer RR : Human globin locus activation region (LAR): role in temporal control. Trends Genet 1990; 6: 219–229.
Grunwald GB : The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules. Curr Opin Cell Biol 1993; 5: 797–805.
Silos SA, Tamai K, Li K et al: Cloning of the gene for human pemphigus vulgaris antigen (Desmoglein 3), a desmosomal cadherin. J Biol Chem 1996; 271: 17504–17511.
Karpati S, Amagai M, Prussick R, Stanley JR : Pemphigus vulgaris antigen is a desmosomal desmoglein. Dermatology 1994; 189: 24–26.
Calvanico NJ, Martins CR, Diaz LA : Characterization of pemphigus foliaceous antigen from human epidermis. J Invest Dermatol 1991; 96: 815–821.
Hashimoto T, Kiyokawa C, Mori O : Human desmocollin 1 (DSC1) is an autoantigen for the subcorneal pustular dermatosis type IgA pemphigus. J Invest Dermatol 1997; 109: 127–131.
Koch PJ, Mahoney MG, Ishikawa H : Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris. J Cell Biol 1997; 137: 1091–1102.
Acknowledgements
We sincerely thank the family members who participated in this study. This work was supported by the Biotechnology Commission of Pakistan – Ministry of Science & Technology, Third World Academy of Sciences (TWAS) – Italy and Pakistan Science Foundation (PSF).
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Rafique, M., Ansar, M., Jamal, S. et al. A locus for hereditary hypotrichosis localized to human chromosome 18q21.1. Eur J Hum Genet 11, 623–628 (2003). https://doi.org/10.1038/sj.ejhg.5201005
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DOI: https://doi.org/10.1038/sj.ejhg.5201005
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