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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1999 May;64(5):1323–1329. doi: 10.1086/302368

Identification of a genetic defect in the hairless gene in atrichia with papular lesions: evidence for phenotypic heterogeneity among inherited atrichias.

E Sprecher 1, R Bergman 1, R Szargel 1, R Friedman-Birnbaum 1, N Cohen 1
PMCID: PMC1377868  PMID: 10205263

Abstract

Recently, we showed that atrichia with papular lesions (APL), a rare inherited form of alopecia, is transmitted as an autosomal recessive trait in a large inbred kindred of Israeli-Arab origin. Furthermore, we mapped the APL locus to a 5-cM region of chromosome 8p12 in this family. The human "hairless" gene is a candidate target gene for the disease mutation because it maps to the APL locus and because it was recently found to be mutated in a related but clinically distinct form of alopecia known as "alopecia universalis" or "congenital alopecia." In the present study, the coding sequence of the hairless gene was compared by reverse transcription-PCR in fibroblast cell lines derived from an affected patient and an unrelated individual. We identified a single-base deletion (3434delC) in the hairless gene that cosegregated with the disease phenotype in the family. This deletion is predicted to cause a frameshift mutation in the highly conserved C-terminal part of the hairless protein, a region putatively involved in the transcription factor activity of the hairless gene product. The present results are indicative of phenotypic heterogeneity in inherited atrichias caused by mutations in the hairless gene, suggesting different roles for the regions mutated in APL and in other forms of congenital atrichia during hair development.

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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. 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]
  5. 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]
  6. Czarnecki N., Stingl G. Atrichia congenita mit Hornzysten - Variante einer partiellen ektodermalen Dysplasie. Z Hautkr. 1980 Feb 15;55(4):210–217. [PubMed] [Google Scholar]
  7. DAMSTE T. J., PRAKKEN J. R. Atrichia with papular lesions; a variant of congenital ectodermal dysplasia. Dermatologica. 1954 Feb;108(2):114–121. doi: 10.1159/000256727. [DOI] [PubMed] [Google Scholar]
  8. Delprat A., Bonafé J. L., Lugardon Y. Atrichie congénitale avec kystes. Ann Dermatol Venereol. 1994;121(11):802–804. [PubMed] [Google Scholar]
  9. Ishii Y., Kusuhara T., Nagata T. Atrichia with papular lesions associated with gastrointestinal polyposis. J Dermatol. 1979 Apr;6(2):111–116. doi: 10.1111/j.1346-8138.1979.tb01888.x. [DOI] [PubMed] [Google Scholar]
  10. Kanzler M. H., Rasmussen J. E. Atrichia with papular lesions. Arch Dermatol. 1986 May;122(5):565–567. [PubMed] [Google Scholar]
  11. Kenue R. K., al-Dhafri K. S. Isolated congenital atrichia in an Omani kindred. Dermatology. 1994;188(1):72–75. doi: 10.1159/000247092. [DOI] [PubMed] [Google Scholar]
  12. Korge B. P., Healy E., Munro C. S., Pünter C., Birch-Machin M., Holmes S. C., Darlington S., Hamm H., Messenger A. G., Rees J. L. A mutational hotspot in the 2B domain of human hair basic keratin 6 (hHb6) in monilethrix patients. J Invest Dermatol. 1998 Nov;111(5):896–899. doi: 10.1046/j.1523-1747.1998.00362.x. [DOI] [PubMed] [Google Scholar]
  13. LOEWENTHAL L. J., PRAKKEN J. R. Atrichia with papular lesions. Dermatologica. 1961 Feb;122:85–89. doi: 10.1159/000255187. [DOI] [PubMed] [Google Scholar]
  14. Misciali C., Tosti A., Fanti P. A., Borrello P., Piraccini B. M. Atrichia and papular lesions: report of a case. Dermatology. 1992;185(4):284–288. doi: 10.1159/000247470. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Sprecher E., Bergman R., Szargel R., Raz T., Labay V., Ramon M., Baruch-Gershoni R., Friedman-Birnbaum R., Cohen N. Atrichia with papular lesions maps to 8p in the region containing the human hairless gene. Am J Med Genet. 1998 Dec 28;80(5):546–550. doi: 10.1002/(sici)1096-8628(19981228)80:5<546::aid-ajmg28>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  17. Thompson C. C., Bottcher M. C. The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8527–8532. doi: 10.1073/pnas.94.16.8527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Zlotogorski A., Horev L., Glaser B. Monilethrix: a keratin hHb6 mutation is co-dominant with variable expression. Exp Dermatol. 1998 Oct;7(5):268–272. doi: 10.1111/j.1600-0625.1998.tb00296.x-i1. [DOI] [PubMed] [Google Scholar]
  22. del Castillo V., Ruiz-Maldonado R., Carnevale A. Atrichia with papular lesions and mental retardation in two sisters. Int J Dermatol. 1974 Sep-Oct;13(5):261–265. doi: 10.1111/j.1365-4362.1974.tb05078.x. [DOI] [PubMed] [Google Scholar]

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