Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia

Schneider, Holm; Faschingbauer, Florian; Schuepbach‐Mallepell, Sonia; Körber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk‐Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; Rascher, Wolfgang; Beckmann, Matthias W.; Schneider, Pascal

doi:10.1097/01.ogx.0000546161.16652.53

Cited by 34 publications

(56 citation statements)

References 4 publications

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“…Dogs, which were treated postnatally, had improved permanent dentition and normalized lacrimation, as well as improved resistance to airway infections and sweating ability (Casal et al 2007; Mauldin et al 2009). Recently, human children were treated prenatally with promising results, too (Schneider et al 2018). The objective of this study was to characterize the ED phenotype in a litter of shorthaired standard Dachshunds, to determine the most likely mode of inheritance after collection of records of relatives, and to unravel the responsible mutation.…”

Section: Introductionmentioning

confidence: 99%

A de novoEDA-variant in a litter of shorthaired standard Dachshunds with X-linked hypohidrotic ectodermal dysplasia

Vasiliadis

Hewicker‐Trautwein

Klotz

et al. 2018

Preprint

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In this study, we present a detailed phenotype description and genetic elucidation of the first case of X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund. This condition is characterized by partial alopecia, missing and malformed teeth and a lack of eccrine sweat glands. Clinical signs including dental X-raying and histopathological findings were consistent with an ectodermal dysplasia. Pedigree analysis supported an X-recessive mode of inheritance. Whole-genome sequencing of one affected puppy and his dam identified a 1-basepair deletion within the ectodysplasin-A gene (CM000039.3:g.54509504delT, PRJEB27789). Sanger sequencing of further family members confirmed the PRJEB27789-variant. Validation in all available family members, 37 unrelated shorthaired standard Dachshunds, 128 Dachshunds from all other breeds and samples from 34 dog breeds revealed the PRJEB27789 variant to be private for this family. Two heterozygous females showed very mild alopecia but normal dentition. Since the dam is demonstrably the only heterozygous animal in the ancestry of the affected animals, we assume that the PRJEB27789-variant arose in the germline of the granddam or in an early embryonic stage of the dam. In conclusion, we detected a very recent de-novo EDA mutation causing X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund.

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Section: Introductionmentioning

confidence: 99%

A de novoEDA-variant in a litter of shorthaired standard Dachshunds with X-linked hypohidrotic ectodermal dysplasia

Vasiliadis

Hewicker‐Trautwein

Klotz

et al. 2018

Preprint

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“…The tissue is placed on a thin filter supported by a metal grid in a dish containing culture medium. Bioengineering of teeth HED phenotype and, interestingly, promising results were reported recently from one trial (21). EDA research is an excellent demonstration that the results of basic biology research may be applied in the future for the prevention of congenital malformations.…”

Section: The Causes and Possible Prevention Of Hypodontia In Humansmentioning

confidence: 85%

From understanding tooth development to bioengineering of teeth

Thesleff

2018

European J Oral Sciences

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Remarkable breakthroughs in the fields of developmental biology and stem cell biology during the last 15 yr have led to a new level of understanding regarding how teeth develop and how stem cells can be programmed. As a result, the possibilities of growing new teeth and of tooth bioengineering have been explored. Currently, a great deal is known about how signaling molecules and genes regulate tooth development, and modern research using transgenic mouse models has demonstrated that it is possible to induce the formation of new teeth by tinkering with the signaling networks that govern early tooth development. A breakthrough in stem cell biology in 2006 opened up the possibility that a patient's own cells can be programmed to develop into pluripotent stem cells and used for building new tissues and organs. At present, active research in numerous laboratories around the world addresses the question of how to program the stem and progenitor cells to develop into tooth-specific cell types. Taken together, the remarkable progress in developmental and stem cell biology is now feeding hopes of growing new teeth in the dental clinic in the not-too-distant future.

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“…More recently, our group reported successful prenatal treatment of XLHED in three boys with EDA null mutations by intra-amniotic administration of a replacement protein that induced the development of functional sweat glands, Meibomian glands and additional tooth germs [13]. The assessment of the natural history of a disease is indispensable for any evaluation of the efficacy of a potential treatment.…”

Section: Introductionmentioning

confidence: 99%

Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study

Wohlfart

Meiller

Hammersen

et al. 2020

Orphanet J Rare Dis

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Background: X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by pathogenic variants of the gene EDA disrupting the prenatal development of ectodermal derivatives. Cardinal symptoms are hypotrichosis, lack of teeth, and hypo-or anhidrosis, but the disease may also evoke other clinical problems. This study aimed at investigating the clinical course of XLHED in early childhood as the basis for an evaluation of the efficacy of potential treatments. Methods: 25 children (19 boys and 6 girls between 11 and 35 months of age) with genetically confirmed XLHED were enrolled in a long-term natural history study. Clinical data were collected both retrospectively using parent questionnaires and medical records (pregnancy, birth, infancy) and prospectively until the age of 60 months. General development, dentition, sweating ability, ocular, respiratory, and skin involvement were assessed by standardized clinical examination and yearly quantitative surveys. Results: All male subjects suffered from persistent anhidrosis and heat intolerance, although a few sweat ducts were detected in some patients. Sweating ability of girls with XLHED ranged from strongly reduced to almost normal. In the male subjects, 1-12 deciduous teeth erupted and 0-8 tooth germs of the permanent dentition became detectable. Tooth numbers were higher but variable in the female group. Most affected boys had no more than three if any Meibomian glands per eyelid, most girls had fewer than 10. Many male subjects developed additional, sometimes severe health issues, such as obstructive airway conditions, chronic eczema, or dry eye disease. Adverse events included various XLHED-related infections, unexplained fever, allergic reactions, and retardation of psychomotor development. Conclusions: This first comprehensive study of the course of XLHED confirmed the early involvement of multiple organs, pointing to the need of early therapeutic intervention.

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Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia

Abstract: This paper has been peer-reviewed but dos not include the final publisher proof-corrections or journal pagination.

Cited by 34 publications

References 4 publications

A de novoEDA-variant in a litter of shorthaired standard Dachshunds with X-linked hypohidrotic ectodermal dysplasia

A de novoEDA-variant in a litter of shorthaired standard Dachshunds with X-linked hypohidrotic ectodermal dysplasia

From understanding tooth development to bioengineering of teeth

Natural history of X-linked hypohidrotic ectodermal dysplasia: a 5-year follow-up study

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