Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia
Abstract
X-linked hypohidrotic ectodermal dysplasia results in abnormal morphogenesis of teeth, hair and eccrine sweat glands. The gene (ED1) responsible for the disorder has been identified, as well as the analogous X-linked gene (Ta) in the mouse. Autosomal recessive disorders, phenotypically indistinguishable from the X-linked forms, exist in humans and at two separate loci (crinkled, cr, and downless, dl) in mice. Dominant disorders, possibly allelic to the recessive loci, are seen in both species (ED3, Dlslk). A candidate gene has recently been identified at the dl locus that is mutated in both dl and Dlslk mutant alleles. We isolated and characterized its human DL homologue, and identified mutations in three families displaying recessive inheritance and two with dominant inheritance. The disorder does not map to the candidate gene locus in all autosomal recessive families, implying the existence of at least one additional human locus. The putative protein is predicted to have a single transmembrane domain, and shows similarity to two separate domains of the tumour necrosis factor receptor (TNFR) family.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mutations in the EDAR gene (2q11-q13), which codes for the EDAR receptor, cause both autosomal forms of hypohidrotic ectodermal dysplasia: ARHED (OMIM 224900) and ADHED (OMIM 129490).
“Mutations in the EDAR gene (2q11-q13) which codes for the EDAR receptor cause both the autosomal forms: ARHED (OMIM 224900) and ADHED (OMIM 129490) [Monreal et al., 1999].”
From Ectodermal dysplasias: Clinical and molecular review (2009) · cites this paper as Monreal et al., 1999
EDA mutations lead to defective development of sweat glands, hair follicles, and dentition.
“These mutations lead to defective development of sweat glands, hair follicles, and dentition.”
From X‐Linked Anhidrotic Ectodermal Dysplasia in A 19‐Year‐Old Male: A Classic Phenotype (2026) · cites this paper as [9]
These mutations were found at identical positions as seen in familial cases of HED in humans.
“These mutations were found at identical positions as seen in familial cases of HED in humans (Figure 3B, E; [11],[12].”
From Zebrafish eda and edar Mutants Reveal Conserved and Ancestral Roles of Ectodysplasin Signaling in Vertebrates (2008) · cites this paper as [11]
Cites
The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death
Smith, C. A., Farrah, T., & Goodwin, R. G. (1994) · Cell · doi:10.1016/0092-8674(94)90372-7 · Cited by 1,909 · see citing works
Fisher, G. H., Rosenberg, F. J., Straus, S. E., Dale, J. K., Middelton, L. A., Lin, A. Y., Strober, W., Lenardo, M. J., & Puck, J. M. (1995) · Cell · doi:10.1016/0092-8674(95)90013-6 · Cited by 1,454 · see citing works
Kere, J., Srivastava, A. K., Montonen, O., Zonana, J., Thomas, N., Ferguson, B., Munoz, F., Morgan, D., Clarke, A., Baybayan, P., et al. (1996) · Nature Genetics · doi:10.1038/ng0895-409 · Cited by 749 · see citing works
Self-citationA Physical Map of 30,000 Human Genes
Deloukas, P., Schuler, G. D., Gyapay, G., Beasley, E., Soderlund, C. A., Rodriguez‐Tomé, P., Hui, L., Matise, T. C., McKusick, K. B., Beckmann, J. S., et al. (1998) · Science · doi:10.1126/science.282.5389.744 · Cited by 704 · see citing works
Frohman, M. A. (1993) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(93)18026-9 · Cited by 498 · see citing works
Construction and Characterization of a Human Bacterial Artificial Chromosome Library
Kim, U., Birren, B. W., Slepak, T. I., et al. (1996) · Genomics · doi:10.1006/geno.1996.0268 · Cited by 455 · see citing works
A radiation hybrid map of the human genome
Gyapay, G. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.3.339 · Cited by 455 · see citing works
Involvement of a novel Tnf receptor homologue in hair follicle induction.
Headon, D. J., & Overbeek, P. A. (1999) · Nature Genetics · doi:10.1038/11943 · Cited by 379 · see citing works
Self-citationSrivastava, A. K., Pispa, J., Hartung, A. J., Du, Y., Ezer, S., Jenks, T., Shimada, T., Pekkanen, M., Mikkola, M. L., Ko, M. S. H., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13069 · Cited by 301 · see citing works
Modularity in the TNF-receptor family
Naismith, J. H., & Sprang, S. R. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(97)01164-x · Cited by 254 · see citing works
Bayés, M., Hartung, A. J., Ezer, S., Pispa, J., Thesleff, I., Srivastava, A. K., & Kere, J. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.11.1661 · Cited by 221 · see citing works
Monreal, A. W., Zonana, J., & Ferguson, B. M. (1998) · The American Journal of Human Genetics · doi:10.1086/301984 · Cited by 206 · see citing works
Self-citationFunctional analysis of the polypyrimidine tract in pre-mRNA splicing
Coolidge, C. J., Seely, R. J., & Patton, J. G. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.4.888 · Cited by 192 · see citing works
Vectorette PCR: a novel approach to genomic walking.Preprint
Arnold, C., & Hodgson, I. J. (1991) · Genome Research · doi:10.1101/gr.1.1.39 · Cited by 189 · see citing works
Bettinardi, A., Brugnoni, D., Quirós-Roldán, E., Malagoli, A., Grutta, S. L., Correra, A., & Notarangelo, L. D. (1997) · Blood · doi:10.1182/blood.v89.3.902 · Cited by 189 · see citing works
Ferguson, B. M. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.9.1589 · Cited by 168 · see citing works
Self-citationHypohidrotic ectodermal dysplasia.
Clarke, A. (1987) · Journal of Medical Genetics · doi:10.1136/jmg.24.11.659 · Cited by 132 · see citing works
Handbook of Mouse Mutations with Skin and Hair Abnormalities
Sundberg, J. P. (2020) · CRC Press eBooks · doi:10.1201/9781003068952 · Cited by 121 · see citing works
Tartaglia, L. A., & Goeddel, D. V. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42833-5 · Cited by 113 · see citing works
Infante, A. J., Britton, H. A., DeNapoli, T. S., Middelton, L. A., Lenardo, M. J., Jackson, C. E., Wang, J., Fleisher, T. A., Straus, S. E., & Puck, J. M. (1998) · The Journal of Pediatrics · doi:10.1016/s0022-3476(98)70102-7 · Cited by 111 · see citing works
Munoz, R., Lestringant, G. G., Sybert, V. P., Frydman, M., Alswaini, A., Frossard, P. M., Jorgenson, R. J., & Zonana, J. (1997) · The American Journal of Human Genetics · doi:10.1086/513905 · Cited by 77 · see citing works
Self-citationCharacterization of the human HOX 7 cDNA and identification of polymorphic markers
Padanilam, B. J., Stadler, H. S., Mills, K. A. M., Mcleod, L. B., Solursh, M., Lee, B., Ramirez, F., Buetow, K. H., & Murray, J. C. (1992) · Human Molecular Genetics · doi:10.1093/hmg/1.6.407 · Cited by 58 · see citing works
Beldjord, C., Lapouméroulie, C., Pagnier, J., et al. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.11.4927 · Cited by 34 · see citing works
High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA) locus.
Zonana, J., Jones, M. A., Browne, D. L., Litt, M. J., Kramer, P. L., Becker, H. W., Brockdorff, N., Rastan, S., Davies, K. P., & Clarke, A. J. (1992) · PubMed · Cited by 33 · see citing works
Self-citationFerguson, B. M., Thomas, N. S., Munoz, F., Morgan, D., Clarke, A. J., & Zonana, J. (1998) · Journal of Medical Genetics · doi:10.1136/jmg.35.2.112 · Cited by 33 · see citing works
Self-citationA Gene for Autosomal Dominant Hypohidrotic Ectodermal Dysplasia (EDA3) Maps to Chromosome 2q11-q13
Ho, L., Williams, M. S., & Spritz, R. A. (1998) · The American Journal of Human Genetics · doi:10.1086/301839 · Cited by 26 · see citing works
YAC rescue of downless locus mutations in mice
Majumder, K., Shawlot, W., Schuster, G., Harrison, W. R., Elder, F. F. B., & Overbeek, P. A. (1998) · Mammalian Genome · doi:10.1007/s003359900884 · Cited by 25 · see citing works
Self-citationFrohman, M. A. (1995) · Elsevier eBooks · doi:10.1016/b978-0-12-765561-1.50048-5 · Cited by 23 · see citing works
Baala, L., Hadj-Rabia, S., Zlotogora, J., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302239 · Cited by 21 · see citing works
Molecular Mechanisms of TNF Receptor-Mediated Signaling
Malek, N. P., Plümpe, J., Kubicka, S., Manns, M. P., & Trautwein, C. (1998) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-80460-1_10 · Cited by 20 · see citing works
Autosomal dominant ectodermal dysplasia.
Jorgenson, R. J., Dowben, J. S., & Sl, D. (1987) · PubMed · Cited by 18 · see citing works
Konrad, M., Saunier, S., Silbermann, F., et al. (1995) · Genomics · doi:10.1006/geno.1995.1272 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The TNF and TNF Receptor Superfamilies
Locksley, R. M., Killeen, N., & Lenardo, M. J. (2001) · Cell · doi:10.1016/s0092-8674(01)00237-9 · Cited by 3,650 · see citing works
Molecular Mechanisms Regulating Hair Follicle Development
Millar, S. E. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01670.x · Cited by 967 · see citing works
Natural selection has driven population differentiation in modern humans
Barreiro, L. B., Laval, G., Quach, H., Patin, E., & Quintana-Murci, L. (2008) · Nature Genetics · doi:10.1038/ng.78 · Cited by 605 · see citing works
Zonana, J., Elder, M. E., Schneider, L. C., Orlow, S. J., Moss, C., Golabi, M., Shapira, S. K., Farndon, P. A., Wara, D. W., Emmal, S. A., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/316914 · Cited by 521 · see citing works
Self-citationGene defect in ectodermal dysplasia implicates a death domain adapter in development
Headon, D. J., Emmal, S. A., Ferguson, B. M., Tucker, A. S., Justice, M. J., Sharpe, P. T., Zonana, J., & Overbeek, P. A. (2001) · Nature · doi:10.1038/414913a · Cited by 378 · see citing works
Self-citationCluzeau, C., Hadj-Rabia, S., Jambou, M., Mansour, S., Guigue, P., Masmoudi, S., Bal, E., Chassaing, N., Vincent, M.-C., Viot, G., et al. (2011) · Human Mutation · doi:10.1002/humu.21384 · Cited by 311 · see citing works
Depew, M. J., Tucker, A. S., & Sharpe, P. T. (2002) · Mouse Development · doi:10.1016/b978-012597951-1/50023-8 · Cited by 259 · see citing works
Fujimoto, A., Kimura, R., Ohashi, J., Omi, K., Yuliwulandari, R., Batubara, L., Mustofa, M. S., Samakkarn, U., Settheetham-Ishida, W., Ishida, T., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddm355 · Cited by 231 · see citing works
Harris, M. P., Rohner, N., Schwarz, H., Perathoner, S., Konstantinidis, P., & Nüsslein-Volhard, C. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000206 · Cited by 224 · see citing works
Adhikari, K., Fuentes-Guajardo, M., Quinto-Sánchez, M., Mendoza-Revilla, J., Camilo Chacón-Duque, J., Acuña-Alonzo, V., Jaramillo, C., Arias, W., Lozano, R. B., Pérez, G. M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11616 · Cited by 200 · see citing works
Self-citationTowards a new classification of ectodermal dysplasias: Classification of EDs
Lamartine, J. (2003) · Clinical and Experimental Dermatology · doi:10.1046/j.1365-2230.2003.01319.x · Cited by 191 · see citing works
Ectodermal dysplasias: Clinical and molecular review
Visinoni, Á. F., Lisboa‐Costa, T., Pagnan, N. A. B., & Chautard‐Freire‐Maia, E. A. (2009) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32864 · Cited by 181 · see citing works
Itin, P. H., & Fistarol, S. K. (2004) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.30033 · Cited by 180 · see citing works
A genome-wide association study identifies multiple loci for variation in human ear morphology
Adhikari, K., Reales, G., Smith, A. J. P., Konka, E., Palmen, J., Quinto-Sanchez, M., Acuña-Alonzo, V., Jaramillo, C., Arias, W., Fuentes, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms8500 · Cited by 95 · see citing works
Self-citationEpidermal patterning and induction of different hair types during mouse embryonic development
Duverger, O., & Morasso, M. I. (2009) · Birth Defects Research Part C: Embryo Today: Reviews · doi:10.1002/bdrc.20158 · Cited by 102 · see citing works
Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus
Bal, E., Baala, L., Cluzeau, C., El Kerch, F., Ouldim, K., Hadj-Rabia, S., Bodemer, C., Munnich, A., Courtois, G., Sefiani, A., et al. (2007) · Human Mutation · doi:10.1002/humu.20500 · Cited by 100 · see citing works
Wohlfart, S., Hammersen, J., & Schneider, H. (2016) · Journal of Human Genetics · doi:10.1038/jhg.2016.75 · Cited by 41 · see citing works
Update of recent findings in genetic hair disorders
Hayashi, R., & Shimomura, Y. (2022) · The Journal of Dermatology · doi:10.1111/1346-8138.16204 · Cited by 22 · see citing works
X‐Linked Anhidrotic Ectodermal Dysplasia in A 19‐Year‐Old Male: A Classic Phenotype
Chapagain, L., Dahal, A., Gupta, P., Pudasaini, P., & Paudel, U. (2026) · Clinical Case Reports · doi:10.1002/ccr3.72650
- Authors
- Monreal, A. W., Ferguson, B. M., Headon, D. J., Street, S. L., Overbeek, P. A., & Zonana, J.
- Affiliations
- Oregon Health & Science University (US)
- Baylor College of Medicine (US)
- Corresponding author
- Ferguson, Betsy M.
- Venue
- Nature Genetics
- Published
- 1999-08
- Volume
- 22
- Issue
- 4
- Pages
- 366-369
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1602743992
- Cited by
- 397
- References
- 32
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 13 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 11 · 2017: 7 · 2016: 9 · 2015: 17 · 2014: 15 · 2013: 13 · 2012: 15
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- National Institutes of Health (5r01ar045316-05)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR45316)
- National Institute of Dental and Craniofacial Research (DE11311, R01DE011311)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- hypohidrotic ectodermal dysplasia, autosomal recessive inheritance, autosomal dominant inheritance, X-linked hypohidrotic ectodermal dysplasia, candidate gene mapping, transmembrane proteins, tooth morphogenesis, hair morphogenesis, eccrine sweat glands
- MeSH terms
- Alleles, Amino Acid Sequence, Animals, Ectodermal Dysplasia, Female, Genes, Dominant, Genes, Recessive, Genetic Markers, Humans, Male, Membrane Proteins, Molecular Sequence Data, Mutation, Pedigree, Tissue Distribution, Sequence Homology, Amino Acid, Receptors, Tumor Necrosis Factor, Physical Chromosome Mapping, Mice, Receptors, Ectodysplasin, Edar Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
