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1.
Acta Vet Scand ; 64(1): 23, 2022 Sep 06.
Article in English | MEDLINE | ID: mdl-36068608

ABSTRACT

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a congenital syndrome of mammals affecting organs and tissues of ectodermal origin characterized by absence or hypoplasia of hair, teeth, and eccrine glands. The disorder has been reported in several species, including humans, mice, dogs and cattle, associated with variants in genes affecting the ectodysplasin pathway, including the X-linked ectodysplasin A (EDA) gene. Until now, nine pathogenic variants have been found in the bovine EDA gene. Here we report a novel variant in EDA in a crossbreed male Belgian Blue calf with HED, and provide an overview of the phenotypic and allelic heterogeneity of EDA-related forms of HED in cattle. CASE PRESENTATION: A 45-day-old male crossbreed British Blue calf was referred with congenital hypotrichosis, oligodontia and omphalitis. On histopathological examination of the nasal planum, nasolabial glands and ducts were not observed. The density of hair follicles was low, and they were small, with a predominance of telogen-phase hairs, and some serocellular crusts. The phenotype of the calf resembled that of HED. Whole-genome sequencing (WGS) was performed and revealed a 21,899 base-pair deletion encompassing the coding exon 2 of EDA, predicted to result in an altered transcript and aberrant protein. CONCLUSIONS: The clinicopathological and genetic findings were consistent with a case of X-linked HED. A very similar EDA deletion has been previously reported in a family of Holstein cattle with HED. The newly identified hemizygous EDA loss-of-function variant is certainly pathogenic and therefore is the genetic cause for the observed phenotype. This case report provides an additional example of the potential of WGS-based precise diagnostics in livestock species such as cattle to increase the diagnostic yield in rare diseases.


Subject(s)
Cattle Diseases , Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Animals , Cattle , Cattle Diseases/genetics , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/veterinary , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodermal Dysplasia 1, Anhidrotic/pathology , Ectodermal Dysplasia 1, Anhidrotic/veterinary , Ectodysplasins/genetics , Exons , Male , Phenotype
2.
Int J Mol Sci ; 23(16)2022 Aug 10.
Article in English | MEDLINE | ID: mdl-36012178

ABSTRACT

Ectodysplasin A (EDA) signaling is initially identified as morphogenic signaling regulating the formation of skin appendages including teeth, hair follicles, exocrine glands in mammals, feathers in birds and scales in fish. Gene mutation in EDA signaling causes hypohidrotic ectodermal dysplasia (HED), a congenital hereditary disease with malformation of skin appendages. Interestingly, emerging evidence suggests that EDA and its receptors can modulate the proliferation, apoptosis, differentiation and migration of cancer cells, and thus may regulate tumorigenesis and cancer progression. More recently, as a newly discovered hepatocyte factor, EDA pathway has been demonstrated to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and type II diabetes by regulating glucose and lipid metabolism. In this review, we summarize the function of EDA signaling from skin appendage development to multiple other diseases, and discuss the clinical application of recombinant EDA protein as well as other potential targets for disease intervention.


Subject(s)
Diabetes Mellitus, Type 2 , Ectodermal Dysplasia 1, Anhidrotic , Animals , Diabetes Mellitus, Type 2/metabolism , Ectodysplasins/genetics , Ectodysplasins/metabolism , Mammals/metabolism , Signal Transduction , Skin/metabolism
3.
J Eur Acad Dermatol Venereol ; 36(10): 1863-1870, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35611639

ABSTRACT

BACKGROUND: In X-linked hypohidrotic ectodermal dysplasia (XLHED), ectodysplasin A1 (EDA1) deficiency results in malformation of hair, teeth and sweat glands. Lack of sweating which can cause life-threatening hyperthermia is amenable to intrauterine therapy with recombinant EDA1. OBJECTIVES: This study aimed at evaluating reproductive decision-making by women with XLHED and at clarifying the potential impact of a prenatal treatment option. METHODS: In a retrospective cross-sectional analysis, a 75-item questionnaire filled in by 50 women with XLHED (age 19-49 years) was assessed. RESULTS: Sixteen women (32%) prevented pregnancies because of the risk to pass on XLHED; 15 considered assisted reproduction for the same reason. Twelve women had a history of miscarriage, stillbirth or abortion, and three women reported on previous abortion of affected fetuses. When imagining to be pregnant, all except one showed interest in prenatal diagnosis of XLHED and in the possibility of treatment before birth. In 13 out of 50 women (26%), XLHED if detected prenatally would have impact on the continuation of pregnancy. Among 35 mothers of at least one affected child, XLHED had rarely been diagnosed during the first pregnancy (17%) but regularly during subsequent pregnancies (77%). Becoming aware of the condition before birth had caused a moral conflict for 50% of these women. Subjects with an affected child less frequently considered assisted reproduction to prevent XLHED (P < 0.05). In 69% of the women who reported an effect of XLHED on family planning, a prenatal treatment option for this disease would influence their decision-making. CONCLUSIONS: Many pregnant XLHED carriers who seek prenatal diagnosis experience moral conflicts. A prenatal treatment option would have strong impact on reproductive decisions, underlining the importance of adequate professional counselling.


Subject(s)
Decision Making , Ectodermal Dysplasia 1, Anhidrotic , Limb Deformities, Congenital , Adult , Cross-Sectional Studies , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins , Female , Humans , Middle Aged , Pregnancy , Reproduction , Retrospective Studies , Young Adult
4.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 57(2): 155-161, 2022 Feb 09.
Article in Chinese | MEDLINE | ID: mdl-35152651

ABSTRACT

Objective: To detect gene mutation in patients with hypohidrotic ectodermal dysplasia (HED) by using whole exome sequencing, to analyze the pathogenicity of the mutations, and to provide reference for the genetic diagnosis of HED patients. Methods: Peripheral blood genomic DNA was extracted from each of the HED patients and their family members collected in Peking University School and Hospital of Stomatology from August 2016 to August 2021. Whole exome sequencing and sanger sequencing were performed to detect gene mutations. Functions of the rare variants after the database filtering were analyzed by bioinformatics tools. Results: Three reported mutations of ectodysplasin A (EDA) gene (c.2T>C, c.161A>G, c.467G>A) and a mutation of ectodysplasin A receptor (EDAR) gene (c.871G>A) were detected by whole genome sequencing in four HED patients, and were verified by Sanger sequencing in four HED families. The EDAR gene mutation founded in this research was reported in HED patients for the first time. Bioinformatics tools predicted that the mutations of EDA gene detected in this study were highly species conserved and disease-causing. The combined annotation dependent depletion (CADD) scores of EDA gene mutations c.2T>C, c.161A>G and c.467G>A were 22.5, 26.3 and 25.5 respectively, and the genomic evolutionary rate profiling (GERP) scores were 2.16, 2.26 and 2.18 respectively. The EDAR gene mutation c.871G>A detected in this study was species conserved and possibly disease-causing. The CADD and GERP scores of EDAR gene mutation c.871G>A were 22.0 and 1.93 respectively. Conclusions: Three reported mutations of EDA gene and a previously unreported mutation of EDAR gene were detected in four HED families. Different mutations of EDA gene and EDAR gene could make different influence on the protein function and lead to the occurrence of HED.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/genetics , Edar Receptor/genetics , Humans , Mutation , Pedigree , Whole Exome Sequencing
5.
Dis Model Mech ; 15(3)2022 03 01.
Article in English | MEDLINE | ID: mdl-35107126

ABSTRACT

In mice, rats, dogs and humans, the growth and function of sebaceous glands and eyelid Meibomian glands depend on the ectodysplasin signalling pathway. Mutation of genes encoding the ligand EDA, its transmembrane receptor EDAR and the intracellular signal transducer EDARADD leads to hypohidrotic ectodermal dysplasia, characterised by impaired development of teeth and hair, as well as cutaneous glands. The rodent ear canal has a large auditory sebaceous gland, the Zymbal's gland, the function of which in the health of the ear canal has not been determined. We report that EDA-deficient mice, EDAR-deficient mice and EDARADD-deficient rats have Zymbal's gland hypoplasia. EdaTa mice have 25% prevalence of otitis externa at postnatal day 21 and treatment with agonist anti-EDAR antibodies rescues Zymbal's glands. The aetiopathogenesis of otitis externa involves infection with Gram-positive cocci, and dosing pregnant and lactating EdaTa females and pups with enrofloxacin reduces the prevalence of otitis externa. We infer that the deficit of sebum is the principal factor in predisposition to bacterial infection, and the EdaTa mouse is a potentially useful microbial challenge model for human acute otitis externa.


Subject(s)
Ear Canal , Ectodermal Dysplasia 1, Anhidrotic , Otitis Externa , Animals , Ectodysplasins , Female , Lactation , Mice
6.
Adv Exp Med Biol ; 1339: 337-340, 2021.
Article in English | MEDLINE | ID: mdl-35023123

ABSTRACT

INTRODUCTION: Hypohidrotic ectodermal dysplasia (HED) is an X-linked recessive disorder, characterised by abnormally developed ectodermal tissues (sweat glands, enamel, hair, nails). HED is caused by mutations of the EDA1 gene (Xq13.1) which codes for ectodysplasin A, a transmembrane signalling protein, which plays a significant role in ectodermal differentiation. Here we present a case of prenatal testing for HED. METHODS: An 11-month-old boy with no family history was clinically diagnosed with HED. Genomic DNA was isolated from the patient's white blood cells, and the possible existence of mutations suspected for HED development was investigated by an NGS gene panel. Total DNA was also isolated from blood samples of his parents. After mutation detection and genetic counselling, a prenatal HED test was performed during the 12th week of the mother's next pregnancy. Embryonic DNA was isolated from a sample of chorionic villi. Parts of the EDA1, AMELX (X chromosome), and SRY (Y chromosome) genes were amplified by PCR, using the corresponding primers. RESULTS: The boy with HED was found to be a hemizygote for the c.595_613del (p. Pro199PhefsTer75) deletion in the EDA1 gene. The fetus was male (XY) that did not carry the pathological mutation. CONCLUSION: The initial diagnosis of a family member with HED in a case with no family history poses the question whether this type of ectodermal dysplasia is autosomal dominant (and the case is due to a de novo mutation), autosomal recessive, or X-linked recessive. Molecular detection of the responsible mutation allows proper genetic counselling, carrier testing, and prevention by prenatal testing.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Ectodermal Dysplasia/diagnosis , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/diagnosis , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Genes, X-Linked/genetics , Genetic Testing , Humans , Infant , Male , Mutation , Pedigree
7.
J Clin Pediatr Dent ; 45(6): 421-427, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34996102

ABSTRACT

BACKGROUND: This case report presents the dimensional changes in dental arches in a patient with hypohidrotic ectodermal dysplasia (HED) after complete denture rehabilitation, with an 18-year follow-up period. CASE REPORT: The patient had complete anodontia and was successfully rehabilitated with conventional complete dentures at 3, 4, 5, 7, 9, 12, 16, and 21 years of age. Each successive denture was larger and contained more and larger teeth so as to accommodate for the increase in the size of the developing jaw. A series of diagnostic casts were used to measure the dimensional changes in the arch length and width of the alveolar ridge. Cast analysis revealed that there was an increase in arch length and width in both the maxilla and mandible over time. Cephalometric analysis of craniofacial development was performed at 21 years of age, and suggested protrusion of the maxilla and mandible. CONCLUSIONS: The absence of teeth due to HED did not affect the dimensional changes in dental arches after complete denture rehabilitation from childhood to adulthood. The prosthetic treatment improved the patient's social integration and enabled the development of normal dietary habits, speech, and facial esthetics, which in turn led to improved quality of life.


Subject(s)
Anodontia , Ectodermal Dysplasia 1, Anhidrotic , Adolescent , Child , Dental Arch , Denture, Complete , Follow-Up Studies , Humans , Quality of Life , Young Adult
8.
J Dermatol ; 49(4): 422-431, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34897795

ABSTRACT

Anhidrotic/hypohidrotic ectodermal dysplasia (A/HED) is a congenital disorder characterized by anhidrosis/hypohidrosis and inadequate hair and dental dysplasia. Large-scale case studies of patients with A/HED have already been conducted overseas, while there has been no large-scale study, but only a few case reports in Japan. Furthermore, an epidemiological study of this disease has not been conducted in Japan to date. The purpose of this study was to investigate the clinical characteristics of A/HED patients, the status of genetic aberrations and complications of A/HED in Japan. Initially, we conducted a physician-initiated questionnaire survey of A/HED patients who visited medical institutions across Japan to investigate their backgrounds, clinical symptoms, genotypes, diagnostic methods and complications of A/HED. We also investigated the presence or absence of various allergic diseases (atopic dermatitis-like skin manifestations, bronchial asthma and food allergies). Questionnaires were also obtained from 26 patients with ectodermal dysplasia (ED) who visited four medical institutions. We compared the incidence of allergic diseases in healthy controls in a similar study to that of patients. Twenty-four of those patients were considered to have A/HED, of which 18 had a confirmed genetic diagnosis and were genotyped. All patients had anhidrosis or hypohidrosis, hair and dental dysplasia, and unique facial appearance; 23 patients had several cutaneous manifestations and seven patients had periorbital pigmentation. In addition, there was a significantly higher incidence of atopic dermatitis-like cutaneous manifestations, bronchial asthma and food allergies in the A/HED patients than in healthy controls. We report the results from a questionnaire survey of 24 patients with A/HED. This is the first report of a large number of A/HED patients in Japan. This study clarifies the status of clinical diagnosis and genetic testing of A/HED patients in Japan, as well as the characteristics of their skin symptoms and allergic complications.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Ectodermal Dysplasia/diagnosis , Ectodermal Dysplasia 1, Anhidrotic/complications , Ectodermal Dysplasia 1, Anhidrotic/epidemiology , Ectodermal Dysplasia 1, Anhidrotic/genetics , Humans , Japan/epidemiology , Prevalence , Surveys and Questionnaires
9.
Am J Med Genet A ; 188(3): 788-805, 2022 03.
Article in English | MEDLINE | ID: mdl-34863015

ABSTRACT

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by mutational inactivation of a developmental pathway responsible for generation of tissues of ectodermal origin. The X-linked form accounts for the majority of HED cases and is caused by Ectodysplasin (EDA) pathogenic variants. We performed a combined analysis of 29 X-linked hypohidrotic ectodermal dysplasia (XLHED) families (including 12 from our previous studies). In addition to the classical triad of symptoms including loss (or reduction) of ectodermal structures, such as hair, teeth, and sweat glands, we detected additional HED-related clinical features including facial dysmorphism and hyperpigmentation in several patients. Interestingly, global developmental delay was identified as an unusual clinical symptom in many patients. More importantly, we identified 22 causal pathogenic variants that included 15 missense, four small in-dels, and one nonsense, splice site, and large deletion each. Interestingly, we detected 12 unique (India-specific) pathogenic variants. Of the 29 XLHED families analyzed, 11 (38%) harbored pathogenic variant localized to the furin cleavage site. A comparison with HGMD revealed significant differences in the frequency of missense pathogenic variants; involvement of specific exons and/or protein domains and transition/transversion ratios. A significantly higher proportion of missense pathogenic variants (33%) localized to the EDA furin cleavage when compared to HGMD (7%), of which p.R155C, p.R156C, and p.R156H were detected in three families each. Therefore, the first comprehensive analysis of XLHED from India has revealed several unique features including unusual clinical symptoms and high frequency of furin cleavage site pathogenic variants.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive , Ectodermal Dysplasia , Limb Deformities, Congenital , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/diagnosis , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Furin/genetics , Humans , Pedigree
10.
J Cell Biochem ; 123(2): 431-449, 2022 02.
Article in English | MEDLINE | ID: mdl-34817077

ABSTRACT

X-linked hypohidrotic dysplasia (XLHED), caused by mutations in the EDA gene, is a rare genetic disease that affects the development and function of the teeth, hair, nails, and sweat glands. The structural and functional consequences of caused by an ectodysplasin-A (EDA) mutations on protein phenotype, stability, and posttranslational modifications (PTMs) have not been well investigated. The present investigation involves five missense mutations that cause XLHED (L56P, R155C, P220L, V251M, and V322A) in different domains of EDA (TM, furin, collagen, and tumor necrosis factor [TNF]) from previously published papers. The deleterious nature of EDA mutant variants was identified using several computational algorithm tools. The point mutations induce major drifts in the structural flexibility of EDA mutant variants and have a negative impact on their stability, according to the 3D protein modeling tool assay. Using the molecular docking technique, EDA/EDA variants were docked to 10 EDA interacting partners, retrieved from the STRING database. We found a novel biomarker CD68 by molecular docking analysis, suggesting all five EDA variants had lower affinity for EDAR, EDA2R, and CD68, implying that they would affect embryonic signaling between the ectodermal and mesodermal cell layers. In silico research such as gene ontology, subcellular localization, protein-protein interaction, and PTMs investigations indicates major functional alterations would occur in EDA variants. According to molecular simulations, EDA variants influence the structural conformation, compactness, stiffness, and function of the EDA protein. Further studies on cell line and animal models might be useful in determining their specific roles in functional annotations.


Subject(s)
Computational Biology , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/chemistry , Ectodysplasins/genetics , Molecular Docking Simulation , Mutation, Missense , Amino Acid Substitution , Ectodermal Dysplasia 1, Anhidrotic/metabolism , Ectodysplasins/metabolism , Humans , Structure-Activity Relationship
12.
Mol Genet Genomic Med ; 9(11): e1824, 2021 11.
Article in English | MEDLINE | ID: mdl-34582123

ABSTRACT

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is mainly caused by ectodysplasin A (EDA) gene mutation. Fetus with genetic deficiency of EDA can be prenatally corrected. This study aimed at revealing the pathogenesis of two HED families and making a prenatal diagnosis for one pregnant female carrier. DESIGNS: Genomic DNA was extracted from two HED patients and sequenced using whole exome sequencing (WES). The detected mutations were confirmed in patients and family members using Sanger sequencing. The expression of soluble ectodysplasin A1 (EDA1) protein was studied by western blot. The transcriptional activity of NF-κB pathway was tested by dual luciferase assay. The genomic DNA of fetus was extracted from shed chorion cells and EDA gene was screened through Sanger sequencing. RESULTS: We identified two novel EDA mutations: c.1136T>C (p.Phe379Ser) and c.[866G>C;868A>T] (p.[Arg289Pro;Ser290Cys]). Further examinations revealed that these two mutated EDA1 proteins showed completely impaired solubility, and the transcriptional NF-κB activation induced by these missense mutant-type EDA1 proteins was significantly reduced compared with wild-type EDA1. Furthermore, the analysis of amniotic fluid samples from a pregnant heterozygote indicated that the fetus was a c.1136T>C mutation female carrier. CONCLUSIONS: This study extended the mutation spectrum of X-linked hypohidrotic ectodermal dysplasia (XLHED) and applied prenatal diagnosis for the pregnant carrier, which can be helpful in genetic counseling, prenatal diagnosis, and intervention for the XLHED family.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodysplasins , Ectodermal Dysplasia 1, Anhidrotic/diagnosis , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Female , Humans , Mutation , Pedigree , Pregnancy , Prenatal Diagnosis
13.
Orphanet J Rare Dis ; 16(1): 373, 2021 09 03.
Article in English | MEDLINE | ID: mdl-34479575

ABSTRACT

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a group of genodermatoses in which deficient ectodysplasin A signalling leads to maldevelopment of skin appendages, various eccrine glands, and teeth. Individuals with HED often have disrupted epithelial barriers and, therefore, were suspected to be more susceptible to coronavirus infection. METHODS: 56 households with at least one member who had coronavirus disease of 2019 (COVID-19) were enrolled in a longitudinal study to compare the course of illness, immune responses, and long-term consequences of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in HED patients (n = 15, age 9-52 years) and control subjects of the same age group (n = 149). RESULTS: In 14 HED patients, mild or moderate typical COVID-19 symptoms were observed that lasted for 4-45 days. Fever during the first days sometimes required external cooling measures. The course of COVID-19 was similar to that in control subjects if patients developed antibodies blocking the SARS-CoV-2 spike protein. Five out of six HED patients with completely abrogated ectodysplasin A signalling (83%) suffered from chronic, in two cases very severe fatigue following COVID-19, while only 25% of HED patients with residual activity of this pathway and 21% of control subjects recovering from COVID-19 experienced postinfectious fatigue. Hair loss after COVID-19 was also more frequent among HED patients (64%) than in the control group (13%). CONCLUSIONS: HED appears to be associated with an increased risk of long-term consequences of a SARS-CoV-2 infection. Preventive vaccination against COVID-19 should be recommended for individuals affected by this rare genetic disorder.


Subject(s)
COVID-19 , Ectodermal Dysplasia 1, Anhidrotic , Fatigue Syndrome, Chronic , Adolescent , Adult , Alopecia , Child , Humans , Longitudinal Studies , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Young Adult
14.
J Dermatol ; 48(10): 1533-1541, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34219261

ABSTRACT

Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by hypohidrosis, hypodontia, and hypotrichosis. Autosomal forms of the disease are caused by mutations in either EDAR or EDARADD. To date, the underlying pathomechanisms for HED resulting from EDARADD mutations have not fully been disclosed. In this study, we performed detailed in vitro analyses in order to characterize three dominantly inherited missense mutations, p.D120Y, p.L122R, and p.D123N, and one recessively inherited missense mutation, p.E152K, in the EDARADD gene. Nuclear factor (NF)-κB reporter assays demonstrated that all the mutant EDARADD showed reduction in activation of NF-κB. Importantly, p.D120Y-, p.L122R-, and p.D123N-mutant EDARADD slightly reduced the NF-κB activity induced by wild-type EDARADD in a dominant negative manner. Co-immunoprecipitation assays showed that all of the mutant EDARADD were capable of binding to EDAR and wild-type EDARADD. Additional co-immunoprecipitation assays revealed that p.D120Y-, p.L122R-, and p.D123N-mutant EDARADD markedly prevented the interaction between EDAR and wild-type EDARADD, which further indicated a dominant negative effect by these mutations. Finally, we found that p.D120Y-, p.L122R-, and p.D123N-mutant EDARADD completely lost the ability to bind with TRAF6, while p.E152K-mutant EDARADD showed a mild reduction in the affinity. Our findings will provide crucial information toward unraveling the molecular mechanisms how EDARADD gene mutations cause the disease.


Subject(s)
Anodontia , Ectodermal Dysplasia 1, Anhidrotic , Edar-Associated Death Domain Protein , Hypohidrosis , Limb Deformities, Congenital , Ectodysplasins , Edar-Associated Death Domain Protein/genetics , Humans , Mutation
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 557-560, 2021 Jun 10.
Article in Chinese | MEDLINE | ID: mdl-34096025

ABSTRACT

OBJECTIVE: To carry out genetic testing for a Chinese patient with X-linked hypohidrotic ectodermal dysplasia (XLHED) and explore its genotype-phenotype correlation. METHODS: Clinical data of the patient was collected. Peripheral blood samples were taken from the patient, his parents and 100 unrelated healthy controls. Genetic variants were detected by using next-generation sequencing using a skin-disease panel through targeted capture and next generation sequencing. Candidate variant was verified by Sanger sequencing. All literature related to genetic testing of XLHED patients in China was searched in the database, and the genotypes and phenotypes of patients in the literature and the correlation between them were statistically analyzed. RESULTS: A novel splice site variant c.655_689del was detected in the patient but not among his parents and the 100 unrelated healthy controls. So far 61 variants of the EDA gene have been identified among Chinese patients with XLHED, which suggested certain degree of genotype-phenotype correlation. CONCLUSION: A novel c.655_689del variant has been identified in the EDA gene, which has expanded the spectrum of EDA gene variant and facilitated delineation of the genotype-phenotype correlation of XLHED.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Child , China , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Genetic Testing , Genotype , Humans , Phenotype
16.
Ital J Pediatr ; 47(1): 128, 2021 Jun 02.
Article in English | MEDLINE | ID: mdl-34078430

ABSTRACT

BACKGROUND: Hypohidrotic Ectodermal Dysplasia (HED) is a genetic disorder which affects structures of ectodermal origin. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of disease. XLHED is characterized by hypotrichosis, hypohydrosis and hypodontia. The cardinal features of classic HED become obvious during childhood. Identification of a hemizygous EDA pathogenic variant in an affected male confirms the diagnosis. CASE PRESENTATION: We report on a male newborn with the main clinical characteristics of the X-linked HED including hypotrichosis, hypodontia and hypohidrosis. Gene panel sequencing identified a new hemizygous missense variant of uncertain significance (VUS) c.1142G > C (p.Gly381Ala) in the EDA gene, located on the X chromosome and inherited from the healthy mother. CONCLUSION: Despite the potential functional impact of VUS remains uncharacterized, our goal is to evaluate the clinical potential consequences of missense VUS on EDA gene. Even if the proband's phenotype is characteristic for classic HED, further reports of patients with same clinical phenotype and the same genomic variant are needed to consider this novel VUS as responsible for the development of HED.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Hemizygote , Mutation, Missense , Chromosomes, Human, X , Humans , Infant, Newborn , Male
17.
J Small Anim Pract ; 62(12): 1127-1130, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34076266

ABSTRACT

In the present report, we describe targeted next-generation sequencing of the EDA gene of a male poodle with a clinical and histopathological diagnosis of X-linked hypohidrotic ectodermal dysplasia. The result was compared with the reference sequence and with the result of the sequencing of a normal dog's EDA gene. No point variant, small deletion or insertion were found in the exons and splice sites, but a transition and a transversion were found in the intron 6' and 3' UTR, respectively. The cause of the dysplasia of the affected dog in this study is neither a point variant nor a small deletion or insertion in the exons and splice sites of the EDA gene. Therefore, patients with phenotype of XLHED may have other types of variants in the EDA gene or variants in other genes of the EDA signalling pathway.


Subject(s)
Dog Diseases , Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Animals , Dog Diseases/genetics , Dogs , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/veterinary , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodermal Dysplasia 1, Anhidrotic/veterinary , Ectodysplasins/genetics , Exons , Male , Mutation , Pedigree , Phenotype
18.
J Clin Ultrasound ; 49(8): 838-840, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33991347

ABSTRACT

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare congenital genetic disorder caused by mutations in the ectodysplasin A gene, resulting in dysplasia or complete absence of teeth, hair, and sweat glands. XLHED is rarely diagnosed prenatally. We describe a case of XLHED diagnosed with prenatal sonography and umbilical cord blood gene testing.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Ectodermal Dysplasia/diagnostic imaging , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/diagnostic imaging , Ectodermal Dysplasia 1, Anhidrotic/genetics , Female , Humans , Mutation , Pregnancy , Sweat Glands , Ultrasonography, Prenatal
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(5): 469-471, 2021 May 10.
Article in Chinese | MEDLINE | ID: mdl-33974258

ABSTRACT

OBJECTIVE: To explore the clinical and genetic characteristics of a child with X-linked hypohidrotic ectodermal dysplasia (XLHED). METHODS: Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents with informed consent and subjected to copy number variation (CNV) analysis and whole exome sequencing (WES). RESULTS: The male infant manifested sparse hair, anhidrosis, anuresis due to polycystic kidney dysplasia, external genital malformation and anal atresia. WES has revealed a 406 bp hemizygous deletion at Xq13 (68 836 147-68 836 553) in the proband, which encompassed exon 1 of the EDA gene. A heterozygous deletion at the same site was detected in the mother, while no deletion or duplication of the site was detected in the father. CONCLUSION: The hemizygous deletion of EDA gene exon 1 probably underlay the ectodermal dysplasia in the proband. Above result has provided a basis for genetic counseling and prenatal diagnosis for the family.


Subject(s)
Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Child , DNA Copy Number Variations , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Genetic Testing , Humans , Infant , Male , Pedigree
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 219-223, 2021 Mar 10.
Article in Chinese | MEDLINE | ID: mdl-33751528

ABSTRACT

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a patient with hypohidrotic ectodermal dysplasia (HED) due to partial deletion of EDA gene. METHODS: The child has presented with HED complicated with epilepsy. Family trio whole exome sequencing (Trio-WES), copy number variation sequencing (CNV-seq), and karyotype analysis were carried out to explore the underlying genetic etiology. RESULTS: The proband, a 7-year-and-8-month-old boy, presented with thin curly hair, thin and sparse eyebrow, xerosis cutis, susceptibility to hyperthermia from childhood, hypohidrosis, sharp/sparse/absent teeth, saddle nose, prominent forehead, auricle adulation and seizure. He was found to have a normal chromosomal karyotype, and no abnormality was found by Trio-WES. Genome-wide CNV-seq revealed a 341.90 kb deletion at Xq13.1q13.1 (chrX: 68 796 566-69 138 468). As verified by PCR-electrophoresis, the deletion has removed part of the EDA gene. The deletion was derived from his mother with normal hair, mild xerosis cutis, and sparse, decidulated and nail-like teeth. The mother was detected with a heterozygous 242.10 kb deletion at Xq13.1q13.1 (chrX: 68 836 154-69 078 250). CONCLUSION: Both the proband and his mother have carried a Xq13.1 microdeletion involving part of the EDA gene. The clinical phenotypes of the mother and the proband were consistent with the clinical characteristics of X-linked recessive HED, for which partial deletion of the EDA gene is probably accountable.


Subject(s)
DNA Copy Number Variations , Ectodermal Dysplasia 1, Anhidrotic , Ectodermal Dysplasia , Child , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Humans , Male , Phenotype
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