X‐linked hypohidrotic ectodermal dysplasia: clinical and molecular genetic analysis of a large Russian family with a synonymous p.Ser267= (c.801A&gt;G) splice site mutation

Миловидова, Т. Б.; Schagina, O. A.; Freire, Matheus; Демина, Н. А.; Filatova, Alexandra; Skoblov, Mikhail; Степанова, Анна; Chuhrova, A L; Polyakov, A. V.

doi:10.1111/jdv.15798

Cited by 2 publications

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References 6 publications

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“…The latter may not be reflected fully by our randomly recruited cohort in which the minority of male subjects with hypomorphic mutations is not represented, but only solid natural history data may allow to predict the severity of XLHED for each known EDA variant. Skewed Xchromosome inactivation is likely to explain phenotypic differences between females with similar EDA variants and has been discussed in a few case reports [31][32][33].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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No evidence for preferential X-chromosome inactivation as the main cause of divergent phenotypes in sisters with X-linked hypohidrotic ectodermal dysplasia

Körber

Schneider

Fleischer

et al. 2021

Orphanet J Rare Dis

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Background X-linked hypohidrotic ectodermal dysplasia (XLHED), a rare genetic disorder, affects the normal development of ectodermal derivatives, such as hair, skin, teeth, and sweat glands. It is caused by pathogenic variants of the gene EDA and defined by a triad of hypotrichosis, hypo- or anodontia, and hypo- or anhidrosis which may lead to life-threatening hyperthermia. Although female carriers are less severely affected than male patients, they display symptoms, too, with high phenotypic variability. This study aimed to elucidate whether phenotypic differences in female XLHED patients with identical EDA genotypes might be explained by deviating X-chromosome inactivation (XI) patterns. Methods Six families, each consisting of two sisters with the same EDA variant and their parents (with either mother or father being carrier of the variant), participated in this study. XLHED-related data like sweating ability, dental status, facial dysmorphism, and skin issues were assessed. We determined the women`s individual XI patterns in peripheral blood leukocytes by the human androgen receptor assay and collated the results with phenotypic features. Results The surprisingly large inter- and intrafamilial variability of symptoms in affected females was not explicable by the pathogenic variants. Our cohort showed no higher rate of nonrandom XI in peripheral blood leukocytes than the general female population. Furthermore, skewed XI patterns in favour of the mutated alleles were not associated with more severe phenotypes. Conclusions We found no evidence for preferential XI in female XLHED patients and no distinct correlation between XLHED-related phenotypic features and XI patterns. Phenotypic variability seems to be evoked by other genetic or epigenetic factors.

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X‐linked hypohidrotic ectodermal dysplasia: clinical and molecular genetic analysis of a large Russian family with a synonymous p.Ser267= (c.801A>G) splice site mutation

Cited by 2 publications

References 6 publications

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

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

No evidence for preferential X-chromosome inactivation as the main cause of divergent phenotypes in sisters with X-linked hypohidrotic ectodermal dysplasia

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