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. 1999 Aug;65(2):413–419. doi: 10.1086/302506

The gene for hypotrichosis of Marie Unna maps between D8S258 and D8S298: exclusion of the hr gene by cDNA and genomic sequencing.

M van Steensel 1, F J Smith 1, P M Steijlen 1, I Kluijt 1, H P Stevens 1, A Messenger 1, H Kremer 1, M G Dunnill 1, C Kennedy 1, C S Munro 1, V R Doherty 1, J A McGrath 1, S P Covello 1, C M Coleman 1, J Uitto 1, W H McLean 1
PMCID: PMC1377939  PMID: 10417283

Abstract

Hypotrichosis of Marie Unna (MU) is an autosomal dominant hair-loss disorder with onset in childhood. A genomewide search for the gene was performed in a large Dutch family using 400 fluorescent microsatellite markers. Linkage was detected with marker D8S258, and analysis of this family and a further British kindred with additional markers in the region gave a combined maximum two-point LOD score of 13.42, with D8S560. Informative recombinants placed the MU gene in a 2.4-cM interval between markers D8S258 and D8S298. Recently, recessive mutations in the hr gene were reported in families with congenital atrichia, and this gene was previously mapped close to the MU interval. By radiation-hybrid mapping, we placed the hr gene close to D8S298 but were unable to exclude it from the MU interval. This, with the existence of the semidominant murine hr allele, prompted us to perform mutation analysis for this gene. Full-length sequencing of hr cDNA obtained from an affected individual showed no mutations. Similarly, screening of all exons of the hr gene amplified from the genomic DNA of an affected individual revealed no mutations. Analysis of expressed sequences and positional cloning of the MU locus is underway.

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Selected References

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  1. Ahmad M., Abbas H., Haque S. Alopecia universalis as a single abnormality in an inbred Pakistani kindred. Am J Med Genet. 1993 Jun 1;46(4):369–371. doi: 10.1002/ajmg.1320460405. [DOI] [PubMed] [Google Scholar]
  2. Ahmad W., Faiyaz ul Haque M., Brancolini V., Tsou H. C., ul Haque S., Lam H., Aita V. M., Owen J., deBlaquiere M., Frank J. Alopecia universalis associated with a mutation in the human hairless gene. Science. 1998 Jan 30;279(5351):720–724. doi: 10.1126/science.279.5351.720. [DOI] [PubMed] [Google Scholar]
  3. Ahmad W., Irvine A. D., Lam H., Buckley C., Bingham E. A., Panteleyev A. A., Ahmad M., McGrath J. A., Christiano A. M. 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 Oct;63(4):984–991. doi: 10.1086/302069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ahmad W., Panteleyev A. A., Henson-Apollonio V., Sundberg J. P., Christiano A. M. Molecular basis of a novel rhino (hr(rhChr)) phenotype: a nonsense mutation in the mouse hairless gene. Exp Dermatol. 1998 Oct;7(5):298–301. doi: 10.1111/j.1600-0625.1998.tb00300.x-i1. [DOI] [PubMed] [Google Scholar]
  5. Ahmad W., Panteleyev A. A., Sundberg J. P., Christiano A. M. Molecular basis for the rhino (hrrh-8J) phenotype: a nonsense mutation in the mouse hairless gene. Genomics. 1998 Nov 1;53(3):383–386. doi: 10.1006/geno.1998.5495. [DOI] [PubMed] [Google Scholar]
  6. Ahmad W., Zlotogorski A., Panteleyev A. A., Lam H., Ahmad M., Faiyaz ul Haque M., Abdallah H. M., Dragan L., Christiano A. M. Genomic organization of the human hairless gene (HR) and identification of a mutation underlying congenital atrichia in an Arab Palestinian family. Genomics. 1999 Mar 1;56(2):141–148. doi: 10.1006/geno.1998.5699. [DOI] [PubMed] [Google Scholar]
  7. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  8. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. BORELLI S. Hypotrichosis congenita hereditaria Marie Unna. Hautarzt. 1954 Jan;5(1):18–22. [PubMed] [Google Scholar]
  10. Bentley-Phillips B., Grace H. J. Hereditary hypotrichosis. A previously undescribed syndrome. Br J Dermatol. 1979 Sep;101(3):331–339. [PubMed] [Google Scholar]
  11. Cachon-Gonzalez M. B., Fenner S., Coffin J. M., Moran C., Best S., Stoye J. P. Structure and expression of the hairless gene of mice. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7717–7721. doi: 10.1073/pnas.91.16.7717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cichon S., Anker M., Vogt I. R., Rohleder H., Pützstück M., Hillmer A., Farooq S. A., Al-Dhafri K. S., Ahmad M., Haque S. Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia. Hum Mol Genet. 1998 Oct;7(11):1671–1679. doi: 10.1093/hmg/7.11.1671. [DOI] [PubMed] [Google Scholar]
  13. Healy E., Holmes S. C., Belgaid C. E., Stephenson A. M., Mclean W. H., Rees J. L., Munro C. S. A gene for monilethrix is closely linked to the type II keratin gene cluster at 12q13. Hum Mol Genet. 1995 Dec;4(12):2399–2402. doi: 10.1093/hmg/4.12.2399. [DOI] [PubMed] [Google Scholar]
  14. Jones J. M., Elder J. T., Simin K., Keller S. A., Meisler M. H. Insertional mutation of the hairless locus on mouse chromosome 14. Mamm Genome. 1993 Nov;4(11):639–643. doi: 10.1007/BF00360900. [DOI] [PubMed] [Google Scholar]
  15. Kere J., Srivastava A. K., Montonen O., Zonana J., Thomas N., Ferguson B., Munoz F., Morgan D., Clarke A., Baybayan P. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet. 1996 Aug;13(4):409–416. doi: 10.1038/ng0895-409. [DOI] [PubMed] [Google Scholar]
  16. Kibar Z., Der Kaloustian V. M., Brais B., Hani V., Fraser F. C., Rouleau G. A. The gene responsible for Clouston hidrotic ectodermal dysplasia maps to the pericentromeric region of chromosome 13q. Hum Mol Genet. 1996 Apr;5(4):543–547. doi: 10.1093/hmg/5.4.543. [DOI] [PubMed] [Google Scholar]
  17. LUDWIG E. Hypotrichosis congenita hereditaria Typ M. Unna. Arch Dermatol Syph. 1953;196(3):261–278. doi: 10.1007/BF00362052. [DOI] [PubMed] [Google Scholar]
  18. Laass M. W., Hennies H. C., Preis S., Stevens H. P., Jung M., Leigh I. M., Wienker T. F., Reis A. Localisation of a gene for Papillon-Lefèvre syndrome to chromosome 11q14-q21 by homozygosity mapping. Hum Genet. 1997 Dec;101(3):376–382. doi: 10.1007/s004390050645. [DOI] [PubMed] [Google Scholar]
  19. McGrath J. A., McMillan J. R., Shemanko C. S., Runswick S. K., Leigh I. M., Lane E. B., Garrod D. R., Eady R. A. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet. 1997 Oct;17(2):240–244. doi: 10.1038/ng1097-240. [DOI] [PubMed] [Google Scholar]
  20. McLean W. H., Rugg E. L., Lunny D. P., Morley S. M., Lane E. B., Swensson O., Dopping-Hepenstal P. J., Griffiths W. A., Eady R. A., Higgins C. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet. 1995 Mar;9(3):273–278. doi: 10.1038/ng0395-273. [DOI] [PubMed] [Google Scholar]
  21. Nöthen M. M., Cichon S., Vogt I. R., Hemmer S., Kruse R., Knapp M., Höller T., Faiyaz ul Haque M., Haque S., Propping P. A gene for universal congenital alopecia maps to chromosome 8p21-22. Am J Hum Genet. 1998 Feb;62(2):386–390. doi: 10.1086/301717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Panteleyev A. A., Ahmad W., Malashenko A. M., Ignatieva E. L., Paus R., Sundberg J. P., Christiano A. M. Molecular basis for the rhino Yurlovo (hr(rhY)) phenotype: severe skin abnormalities and female reproductive defects associated with an insertion in the hairless gene. Exp Dermatol. 1998 Oct;7(5):281–288. doi: 10.1111/j.1600-0625.1998.tb00298.x-i1. [DOI] [PubMed] [Google Scholar]
  23. Panteleyev A. A., Paus R., Ahmad W., Sundberg J. P., Christiano A. M. Molecular and functional aspects of the hairless (hr) gene in laboratory rodents and humans. Exp Dermatol. 1998 Oct;7(5):249–267. doi: 10.1111/j.1600-0625.1998.tb00295.x-i1. [DOI] [PubMed] [Google Scholar]
  24. Peachey R. D., Wells R. S. Hereditary hypotrichosis (Marie Unna type). Trans St Johns Hosp Dermatol Soc. 1971;57(1):157–166. [PubMed] [Google Scholar]
  25. Robinson H. C., Russell M. L., Csokonay W. M. Japanese encephalitis vaccine and adverse effects among travellers. Can Dis Wkly Rep. 1991 Aug 10;17(32):173-4, 177. [PubMed] [Google Scholar]
  26. Solomon L. M., Esterly N. B., Medenica M. Hereditary trichodysplasia: Marie Unna's hypotrichosis. J Invest Dermatol. 1971 Dec;57(6):389–400. doi: 10.1111/1523-1747.ep12293186. [DOI] [PubMed] [Google Scholar]
  27. Spiegl B., Hundeiker M. Hypotrichosis congenita hereditaria Autosomal dominante generalisierte Hypotrichose mit Pili torti (Hypotrichosis congenita hereditaria Marie Unna). Fortschr Med. 1979 Nov 22;97(44):2018–2022. [PubMed] [Google Scholar]
  28. Stelzner K. F. Four dominant autosomal mutations affecting skin and hair development in the mouse. J Hered. 1983 May-Jun;74(3):193–196. doi: 10.1093/oxfordjournals.jhered.a109761. [DOI] [PubMed] [Google Scholar]
  29. Stevanović D. V. Hereditary hypotrichosis congenita: Marie Unna type. Br J Dermatol. 1970 Sep;83(3):331–337. doi: 10.1111/j.1365-2133.1970.tb15711.x. [DOI] [PubMed] [Google Scholar]
  30. Winter H., Rogers M. A., Gebhardt M., Wollina U., Boxall L., Chitayat D., Babul-Hirji R., Stevens H. P., Zlotogorski A., Schweizer J. A new mutation in the type II hair cortex keratin hHb1 involved in the inherited hair disorder monilethrix. Hum Genet. 1997 Dec;101(2):165–169. doi: 10.1007/s004390050607. [DOI] [PubMed] [Google Scholar]
  31. Winter H., Rogers M. A., Langbein L., Stevens H. P., Leigh I. M., Labrèze C., Roul S., Taieb A., Krieg T., Schweizer J. Mutations in the hair cortex keratin hHb6 cause the inherited hair disease monilethrix. Nat Genet. 1997 Aug;16(4):372–374. doi: 10.1038/ng0897-372. [DOI] [PubMed] [Google Scholar]
  32. Wirth G., Bindewald I., Küster W., Goerz G. Hypotrichosis congenita hereditaria Marie Unna. Hautarzt. 1985 Oct;36(10):577–580. [PubMed] [Google Scholar]
  33. Zlotogorski A., Ahmad W., Christiano A. M. Congenital atrichia in five Arab Palestinian families resulting from a deletion mutation in the human hairless gene. Hum Genet. 1998 Oct;103(4):400–404. doi: 10.1007/s004390050840. [DOI] [PubMed] [Google Scholar]

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