Abstract
X-linked hypohidrotic ectodermal dysplasia (EDA) has been localized to the Xq12-q13.1 region. A panel of genomic DNA samples from 80 unrelated males with EDA has been screened for deletions at seven genetic loci within the Xq12-13 region. A single individual was identified with a deletion at the DXS732 locus by hybridization with the mouse genomic probe pcos169E/4. This highly conserved DNA probe is from locus DXCrc169, which is tightly linked to the Ta locus, the putative mouse homologue of EDA. The proband had the classical phenotype of EDA, with no other phenotypic abnormalities, and a normal cytogenetic analysis. A human genomic DNA clone, homologous to pcos169E/4, was isolated from a human X-chromosome cosmid library. On hybridization with the cosmid, the proband was found to be only partially deleted at the DXS732 locus, with a unique junctional fragment identified in the proband and in three of his maternal relatives. This is the first determination of carrier status for EDA in females, by direct mutation analysis. Failure to detect deletion of the other loci tested in the proband suggests that the DXS732 locus is the closest known locus to the EDA gene. Since the DXS732 locus contains a highly conserved sequence, it must be considered to be a candidate locus for the EDA gene itself.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blecher S. R. Anhidrosis and absence of sweat glands in mice hemizygous for the Tabby gene: supportive evidence for the hypothesis of homology between Tabby and human anhidrotic (hypohidrotic) ectodermal dysplasia (Christ-Siemens-Touraine syndrome). J Invest Dermatol. 1986 Dec;87(6):720–722. doi: 10.1111/1523-1747.ep12456718. [DOI] [PubMed] [Google Scholar]
- Brockdorff N., Kay G., Cattanach B. M., Rastan S. Molecular genetic analysis of the Ta25H deletion: evidence for additional deleted loci. Mamm Genome. 1991;1(3):152–157. doi: 10.1007/BF00351061. [DOI] [PubMed] [Google Scholar]
- Brockdorff N., Kay G., Smith S., Keer J. T., Hamvas R. M., Brown S. D., Rastan S. High-density molecular map of the central span of the mouse X chromosome. Genomics. 1991 May;10(1):17–22. doi: 10.1016/0888-7543(91)90478-w. [DOI] [PubMed] [Google Scholar]
- Brockdorff N., Montague M., Smith S., Rastan S. Construction and analysis of linking libraries from the mouse X chromosome. Genomics. 1990 Aug;7(4):573–578. doi: 10.1016/0888-7543(90)90201-5. [DOI] [PubMed] [Google Scholar]
- Cattanach B. M., Rasberry C., Evans E. P., Dandolo L., Simmler M. C., Avner P. Genetic and molecular evidence of an X-chromosome deletion spanning the tabby (Ta) and testicular feminization (Tfm) loci in the mouse. Cytogenet Cell Genet. 1991;56(3-4):137–143. doi: 10.1159/000133070. [DOI] [PubMed] [Google Scholar]
- Clarke A., Phillips D. I., Brown R., Harper P. S. Clinical aspects of X-linked hypohidrotic ectodermal dysplasia. Arch Dis Child. 1987 Oct;62(10):989–996. doi: 10.1136/adc.62.10.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crawford P. J., Aldred M. J., Clarke A. Clinical and radiographic dental findings in X linked hypohidrotic ectodermal dysplasia. J Med Genet. 1991 Mar;28(3):181–185. doi: 10.1136/jmg.28.3.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Limon J., Filipiuk J., Nedoszytko B., Mrózek K., Castrén M., Larramendy M., Roszkiewicz J. X-linked anhidrotic ectodermal dysplasia and de novo t(X;1) in a female. Hum Genet. 1991 Jul;87(3):338–340. doi: 10.1007/BF00200916. [DOI] [PubMed] [Google Scholar]
- Litt M., White R. L. A highly polymorphic locus in human DNA revealed by cosmid-derived probes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6206–6210. doi: 10.1073/pnas.82.18.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nizetić D., Zehetner G., Monaco A. P., Gellen L., Young B. D., Lehrach H. Construction, arraying, and high-density screening of large insert libraries of human chromosomes X and 21: their potential use as reference libraries. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3233–3237. doi: 10.1073/pnas.88.8.3233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turleau C., Niaudet P., Cabanis M. O., Plessis G., Cau D., de Grouchy J. X-linked hypohidrotic ectodermal dysplasia and t(X;12) in a female. Clin Genet. 1989 Jun;35(6):462–466. doi: 10.1111/j.1399-0004.1989.tb02973.x. [DOI] [PubMed] [Google Scholar]
- Weber J. L., Kwitek A. E., May P. E., Polymeropoulos M. H., Ledbetter S. Dinucleotide repeat polymorphisms at the DXS453, DXS454 and DXS458 loci. Nucleic Acids Res. 1990 Jul 11;18(13):4037–4037. doi: 10.1093/nar/18.13.4037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zonana J., Clarke A., Sarfarazi M., Thomas N. S., Roberts K., Marymee K., Harper P. S. X-linked hypohidrotic ectodermal dysplasia: localization within the region Xq11-21.1 by linkage analysis and implications for carrier detection and prenatal diagnosis. Am J Hum Genet. 1988 Jul;43(1):75–85. [PMC free article] [PubMed] [Google Scholar]
- Zonana J., Jones M., Browne D., Litt M., Kramer P., Becker H. W., Brockdorff N., Rastan S., Davies K. P., Clarke A. High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA) locus. Am J Hum Genet. 1992 Nov;51(5):1036–1046. [PMC free article] [PubMed] [Google Scholar]
- Zonana J., Sarfarazi M., Thomas N. S., Clarke A., Marymee K., Harper P. S. Improved definition of carrier status in X-linked hypohidrotic ectodermal dysplasia by use of restriction fragment length polymorphism-based linkage analysis. J Pediatr. 1989 Mar;114(3):392–399. doi: 10.1016/s0022-3476(89)80556-6. [DOI] [PubMed] [Google Scholar]