Genetic testing and genotype-phenotype analysis for a child with X-linked hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

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.

Clinical and genetic analysis of a child with X-linked hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

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.

Phenotypic and genetic analysis of a case with hypohidrotic ectodermal dysplasia due to Xq13.1 microdeletion / 中华医学遗传学杂志

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.

Displasia ectodérmica hipohidrótica ligada al cromosoma X de novo por variante recurrente en un paciente mexicano / X-linked hypohidrotic ectodermal dysplasia by a de novo recurrent variant in a Mexican patient

Resumen Introducción: Las displasias ectodérmicas son un grupo de genodermatosis que se caracterizan por distrofia de las estructuras derivadas del ectodermo. De ellas, la variedad más común es la hipohidrótica, con una incidencia de 7/100,000 nacidos vivos observada en todos los grupos étnicos. La displasia ectodérmica hipohidrótica tiene distintas etiologías. La presentación más frecuente es la asociada a un patrón de herencia ligado al cromosoma X, causada por variantes patogénicas del gen EDA en Xq13.1. EDA codifica a la ectodisplasina A, una molécula de señalización que participa en la comunicación epitelio-mesénquima durante el desarrollo de la piel y los anexos. Caso clínico: Varón de 6 años con las características clínicas cardinales de la displasia ectodérmica hipohidrótica ligada al cromosoma X (DEHLX), que incluyen hipotricosis, oligodoncia e hipohidrosis. El análisis del gen EDA por secuenciación directa mostró la presencia de la variante patogénica c.466C>T, p.Arg156Cys, rs132630313 con presentación de novo en el paciente. Esta variante ya ha sido reportada en diferentes poblaciones, incluyendo familias mexicanas, y constituye un punto caliente para mutación en EDA. Se analizaron los hallazgos clínicos, la etiología y el manejo de la DEHLX, en la que de manera reciente se ha planteado la posibilidad de otorgar tratamiento prenatal para prevenir sus manifestaciones clínicas. Conclusiones: Se pone de relevancia que el análisis molecular en pacientes con DEHLX corrobora el diagnóstico clínico y permite brindar asesoramiento genético con bases moleculares.

Abstract Background: Ectodermal dysplasias are a group of genodermatoses characterized by dystrophy of ectodermal derived structures. The most frequent presentation of the ectodermal dysplasias is the hypohidrotic type, which has an incidence of 7/100,000 newborns and has been described in all ethnic groups. The hypohidrotic ectodermal dysplasia (HED) has different etiologies, and it is more frequently associated with an X-linked pattern of inheritance caused by pathogenic variants of the EDA gene in Xq13.1. EDA encodes the protein ectodisplasin A, a signal molecule which participates in epithelium and mesenchymal development of the skin. Case report: A 6 year-old male patient with the main clinical characteristics of the X-linked HED including hypotrichosis, hypodontia and hypohidrosis. The direct sequencing analysis of EDA in our patient detected a de novo pathogenic variant, c.466C>T, p.Arg156Cys, rs132630313. This variant has been previously described in different ethnic groups, including Mexican families, and is considered a mutational hotspot. The clinical characteristics, etiology and management of the X-linked HED, including the possibility of prenatal therapy in order to avoid the clinical manifestations are discussed. Conclusions: The molecular analysis in patients with X-linked HED is of relevance, as it enables to confirm the clinical diagnosis and also, it allows a genetic assessment with molecular bases.

Prenatal diagnosis of a fetus with X-linked hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

OBJECTIVE@#To detect variant of EDA gene in a fetus with absence of germ teeth detected by prenatal ultrasonography.@*METHODS@#Clinical data and amniotic fluid and peripheral venous blood samples of the pregnant woman were collected for the analysis. Following extraction of genome DNA, the coding regions of the EDA gene were amplified by PCR and subjected to next-generation sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#The pregnant woman was found to carry a heterozygous c.574G>A variant in the EDA gene, for which the fetus was hemizygous. Bioinformatic analysis suggested the variant to be pathogenic.@*CONCLUSION@#Combined ultrasonographic and genetic findings suggested the fetus is affected with X-linked hypohidrotic ectodermal dysplasia due to pathogenic variant of the EDA gene.

Genetic analysis of a case with ectodermal dysplasia using whole exome sequencing / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic cause of a patient suspected for congenital ectodermal dysplasia with repeated hyperthermia and to assess the reproductive risk for his family.@*METHODS@#Medical whole-exome sequencing (WES) were used to detect single-nucleotide variations and low-coverage massively parallel copy number variation sequencing (CNV-seq) were employed to verify suspected CNVs. PCR and real-time quantitative PCR were applied to confirm the deletion of EDA gene.@*RESULTS@#The results of WES suggested that the patient carried a hemizygous deletion for chrX:69 243 016-69 395 730. CNV-seq indicated that the patient carried a deletion of approximately 0.12 Mb on Xq13.1, which encompassed the EDA gene. The PCR results confirmed that there was a hemizygous deletion of exons 3 to 8 of the EDA gene. The same deletion was not found in his mother.@*CONCLUSION@#The congenital ectodermal dysplasia of the patient may be attributed to deletion of exons 3 to 8 of the EDA gene, which could be de novo or derive from germline mosaicism of his mother. The WES and CNV-seq are of great value for the diagnosis of rare diseases.

Detection of EDA gene mutation and phenotypic analysis in patients with hypohidrotic ectodermal dysplasia / 北京大学学报(医学版)

OBJECTIVE@#To detect the ectodysplasin A (EDA) gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with EDA gene mutation.@*METHODS@#Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the EDA gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of EDA gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each EDA gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with EDA gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared.@*RESULTS@#Eight out of twelve HED families were identified to carry EDA gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with EDA gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (P>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence.@*CONCLUSION@#This study detected novel EDA gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of EDA gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.

Expression patterns of ectodysplasin and ectodysplasin receptor during early dental development in zebrafish / 华西口腔医学杂志

OBJECTIVE@#This study aims to study the expression patterns of ectodysplasin (EDA) and ectodysplasin receptor (EDAR) during the early development of zebrafish and provide a foundation for further research of the Eda signaling pathway in tooth development.@*METHODS@#Total RNA was extracted from zebrafish embryos at 48 hours postfertilization (hpf) and then reverse transcribed for cDNA library generation. The corresponding RNA polymerase was selected for the synthesis of the digoxin-labeled antisense mRNA probe of zebrafish pharyngeal tooth specific marker dlx2b and Eda signaling-associated genes eda and edar in vitro. The three sequences were ligated into a pGEMT vector with a TA cloning kit, and polymerase chain reaction (PCR) was applied to linearize the plasmid. The resultant PCR sequences were used as templates for synthesizing Dig-labeled mRNA probe dlx2b, eda, and edar. Zebrafish embryos were collected at 36, 48, 56, 60, 72, and 84 hpf, then whole mount in situ hybridization was performed for the detection of eda and edar expression patterns. Then, their expression patterns at 72 hpf were compared with the expression pattern of dlx2b.@*RESULTS@#The mRNA antisense probes of dlx2b, eda, and edar were successfully obtained. The positive signals of eda and edar were observed in zebrafish pharyngeal tooth region at 48-72 hpf and thus conform to the signals of dlx2b in the positive regions.@*CONCLUSIONS@#The ligand eda and edar, which are associated with the Eda signaling pathway, are strongly expressed only at the pharyngeal tooth region in zebrafish from tooth initiation to the morphogenesis stage. Thus, the Eda signaling pathway may be involved in the regulation of the early development of zebrafish pharyngeal teeth.

In Vivo Validation Model of a Novel Anti-Inflammatory Scaffold in Interleukin-10 Knockout Mouse

BACKGROUND: We fabricated anti-inflammatory scaffold using Mg(OH)2-incorporated polylactic acid-polyglycolic acid copolymer (MH-PLGA). To demonstrate the anti-inflammatory effects of the MH-PLGA scaffold, an animal model should be sensitive to inflammatory responses. The interleukin-10 knockout (IL-10 KO) mouse is a widely used bowel disease model for evaluating inflammatory responses, however, few studies have evaluated this mouse for the anti-inflammatory scaffold. METHODS: To compare the sensitivity of the inflammatory reaction, the PLGA scaffold was implanted into IL-10 KO and C57BL/6 mouse kidneys. Morphology, histology, immunohistochemistry, and gene expression analyses were carried out at weeks 1, 4, 8, and 12. The anti-inflammatory effect and renal regeneration potency of the MH-PLGA scaffold was also compared to those of PLGA in IL-10 KO mice. RESULTS: The PLGA scaffold-implanted IL-10 KO mice showed kidneys relatively shrunken by fibrosis, significantly increased inflammatory cell infiltration, high levels of acidic debris residue, more frequent CD8-, C-reactive protein-, and ectodysplasin A-positive cells, and higher expression of pro-inflammatory and fibrotic factors compared to the control group. The MH-PLGA scaffold group showed lower expression of pro-inflammatory and fibrotic factors, low immune cell infiltration, and significantly higher expression of anti-inflammatory factors and renal differentiation related genes compared to the PLGA scaffold group. CONCLUSION: These results indicate that the MH-PLGA scaffold had anti-inflammatory effects and high renal regeneration potency. Therefore, IL-10 KO mice are a suitable animal model for in vivo validation of novel anti-inflammatory scaffolds.

Neuroprotective effects of erythropoietin on rat retinas subjected to oligemia

OBJECTIVES: Erythropoietin may have neuroprotective potential after ischemia of the central nervous system. Here, we conducted a study to characterize the protective effects of erythropoietin on retinal ganglion cells and gliotic reactions in an experimentally induced oligemia model. METHODS: Rats were subjected to global oligemia by bilateral common carotid artery occlusion and then received either vehicle or erythropoietin via intravitreal injection after 48 h; they were euthanized one week after the injection. The densities of retinal ganglion cells and contents of glial fibrillary acidic protein (astrocytes/Müller cells) and cluster of differentiation 68 clone ED1 (microglia/macrophages), assessed by fluorescence intensity, were evaluated in frozen retinal sections by immunofluorescence and epifluorescence microscopy. RESULTS: Retinal ganglion cells were nearly undetectable one week after oligemia compared with the sham controls; however, these cells were partially preserved in erythropoietin-treated retinas. The contents of glial fibrillary acidic protein and cluster of differentiation 68 clone ED1, markers for reactive gliosis, were significantly higher in retinas after bilateral common carotid artery occlusion than those in both sham and erythropoietin-treated retinas. CONCLUSIONS: The number of partially preserved retinal ganglion cells in the erythropoietin-treated group suggests that erythropoietin exerts a neuroprotective effect on oligemic/ischemic retinas. This effect could be related to the down-modulation of glial reactivity, usually observed in hypoxic conditions, clinically observed during glaucoma or retinal artery occlusion conditions. Therefore, glial reactivity may enhance neurodegeneration in hypoxic conditions, like normal-tension glaucoma and retinal ischemia, and erythropoietin is thus a candidate to be clinically applied after the detection of decreased retinal blood flow.

Estudio clínico y molecular en un escolar con displasia ectodérmica hipohidrótica ligada al X / Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia

Las displasias ectodérmicas comprenden más de 200 entidades clínicamente distintivas, las cuales afectan, al menos, dos estructuras derivadas del ectodermo, que incluyen la piel, el pelo, las unas, los dientes, las glándulas sudoríparas y sebáceas. La displasia ectodérmica hipohidrótica ligada al X es el tipo más frecuente y es causada por mutación del gen EDA, que codifica la ectodisplasina-A. Su frecuencia es menor de 1 en 100000 individuos y se caracteriza clínicamente por presentar hipodoncia, hipohidrosis, hipotricosis y alteraciones oculares. Se expone el caso de un escolar evaluado de forma multidisciplinaria con diagnóstico clínico y molecular de displasia ectodérmica hipohidrótica ligada al X con mutación tipo cambio de sentido c.1133C>,T, p.T378M, en el gen EDA.

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia: a case-control study in southwest China

Our research aimed to look into the clinical traits and genetic mutations in sporadic non-syndromic anodontia and to gain insight into the role of mutations of PAX9, MSX1, AXIN2 and EDA in anodontia phenotypes, especially for the PAX9. Material and Methods The female proband and her family members from the ethnic Han families underwent complete oral examinations and received a retrospective review. Venous blood samples were obtained to screen variants in the PAX9, MSX1, AXIN2, and EDA genes. A case-control study was performed on 50 subjects with sporadic tooth agenesis (cases) and 100 healthy controls, which genotyped a PAX9 gene polymorphism (rs4904210). Results Intra-oral and panoramic radiographs revealed that the female proband had anodontia denoted by the complete absence of teeth in both the primary and secondary dentitions, while all her family members maintained normal dentitions. Detected in the female proband were variants of the PAX9 and AXIN2 including A240P (rs4904210) of the PAX9, c.148C>T (rs2240308), c.1365A>G (rs9915936) and c.1386C>T (rs1133683) of the AXIN2. The same variants were present in her unaffected younger brother. The PAX9 variations were in a different state in her parents. Mutations in the MSX1 and EDA genes were not identified. No significant diferences were found in the allele and genotype frequencies of the PAX9 polymorphism between the controls and the subjects with sporadic tooth agenesis. Conclusions These results suggest that the association of A240P with sporadic tooth agenesis still remains obscure, especially for different populations. The genotype/phenotype correlation in congenital anodontia should be verified. .

Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury

PURPOSE: This study was performed to evaluate the long-term effects and safety of intratracheal (IT) transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in neonatal hyperoxic lung injury at postnatal day (P)70 in a rat model. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (90% oxygen) within 10 hours after birth and allowed to recover at room air until sacrificed at P70. In the transplantation groups, hUCB-MSCs (5x10(5)) were administered intratracheally at P5. At P70, various organs including the heart, lung, liver, and spleen were histologically examined, and the harvested lungs were assessed for morphometric analyses of alveolarization. ED-1, von Willebrand factor, and human-specific nuclear mitotic apparatus protein (NuMA) staining in the lungs and the hematologic profile of blood were evaluated. RESULTS: Impaired alveolar and vascular growth, which evidenced by an increased mean linear intercept and decreased amount of von Willebrand factor, respectively, and the hyperoxia-induced inflammatory responses, as evidenced by inflammatory foci and ED-1 positive alveolar macrophages, were attenuated in the P70 rat lungs by IT transplantation of hUCB-MSCs. Although rare, donor cells with human specific NuMA staining were persistently present in the P70 rat lungs. There were no gross or microscopic abnormal findings in the heart, liver, or spleen, related to the MSCs transplantation. CONCLUSION: The protective and beneficial effects of IT transplantation of hUCB-MSCs in neonatal hyperoxic lung injuries were sustained for a prolonged recovery period without any long-term adverse effects up to P70.

Identification of a novel c.822 G>T mutation of EDA gene in a Chinese family with X-linked hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of ectodysplasin A (EDA) gene in a Chinese family affected with X-linked hypohidrotic ectodermal dysplasia.</p><p><b>METHODS</b>Blood samples were collected from the affected male proband, his family members and 103 unrelated individuals. Following extraction of genomic DNA, coding sequence of the EDA gene was amplified with PCR, and DNA sequencing was performed to detect potential mutation.</p><p><b>RESULTS</b>A novel missense mutation, c.822G>T (p.W274C), was identified in exon 7 of the EDA gene in the proband, whilst his mother was found to be a heterozygous carrier. The same mutation was also found in 5 other family members including one affected male and four females, but was absent in unaffected males and 103 unrelated individuals.</p><p><b>CONCLUSION</b>A c.822G>T mutation in exon 7 of the EDA gene probably underlies the disease in this Chinese family.</p>

Analysis of EDA gene mutation for a family affected with X-linked hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of EDA gene for a Chinese family affected with X-linked hypohidrotic ectodermal dysplasia (XLHED).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood of the proband, his relatives and 50 non-related healthy controls. Exonic sequences of the EDA gene were subjected to polymerase chain reaction amplification and direct sequencing.</p><p><b>RESULTS</b>A c.467G> A mutation (R156H) was detected in exon 3 of the EDA gene in the proband, his mother, 2 uncles, and 1 aunt. The same mutation was not detected in the 50 non-related healthy controls.</p><p><b>CONCLUSION</b>A c.467G>A mutation of the EDA gene probably underlies the disease in the family.</p>

Molecular genetics study of ED1 gene for two X-linked hypohidrotic ectodermal dysplasia families / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide genetic diagnosis and counseling for patients from two families affected with X-linked hypohidrotic ectodermal dysplasia.</p><p><b>METHODS</b>Potential mutation of the ED1 gene was screened by DNA sequencing. For family 1, multiplex ligation-dependent probe amplification (MLPA) analysis and haplotyping of ED1 gene were also carried out for prenatal diagnosis.</p><p><b>RESULTS</b>For the patient from family 1, deletion of the exon 1 of the ED1 gene and 2 short tandem repeat(STR) sites (DXS8269 and DXS1422) were detected. His daughter was carrier of the deletion. Upon prenatal diagnosis, the fetus was confirmed to be a normal male, for whom the haplotype of ED1 gene has differed from that of the proband. In family 2, a c.463C>T mutation in exon 3 of the ED1 gene was detected in the proband, whose mother was heterozygous for the same mutation.</p><p><b>CONCLUSION</b>The deletion (exon 1) and missense (R155C) mutation in ED1 gene have probably underlied the disease in the two families. During prenatal diagnosis, it may be necessary to obtain precise results through combining mutation detection and haplotype analysis of the ED1 gene.</p>

Detection of ED1 gene mutations in six pedigrees with hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutations of ED1 gene in six pedigrees with hypohidrotic ectodermal dysplasia (HED), and to provide genetic counseling and prenatal diagnosis.</p><p><b>METHODS</b>Eight coding exons of ED1 gene of patients with clinically diagnosed HED and their relatives were amplified by polymerase chain reaction (PCR). The products were further analyzed by direct sequencing.</p><p><b>RESULTS</b>Various mutations of ED1 gene were detected, which included R153C, A349T, G299S, A349T and X392Q. Heterozygous double peaks at the same position were found in female carriers. Deletion of exon 9 was detected in one pedigree. R153C, X392Q and deletion of exon 9 were first identified in ethnic Han Chinese.</p><p><b>CONCLUSION</b>The identified mutations of ED1 gene may be responsible for the disease. Genetic counseling, prenatal diagnosis and carrier screening are now available for these families.</p>

Mutación en el gen EDA1, Ala349Thr en paciente con displasia ectodérmica hipohidrótica ligada a X / Mutation in the ED1, Ala349Thr in a patient with X-linked hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a very rare disease characterized by the absence of eccrine glands, dry skin, scanty hair, and dental abnormalities. It is caused by mutations within the ED1 gene, which encodes a protein, ectodysplasin-A (EDA). Clinical characteristic are frontal bossing, saddle nose, pointed chin, a prominent supraorbital ridge with periorbital hyperpigmenta-tion, and anodontia. Those affected show great intolerance to heat. We report the first Mexican 2-year-old boy with an Ala349Thr missense mutation from Tamaulipas, México.

Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with severe full-thickness burn injury suffer from their inability to maintain body temperature through perspiration because the complete destructed sweat glands can not be regenerated. Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent an ideal stem-cell source for cell therapy because of their easy purification and multipotency. In this study, we attempted to induce human BM-MSCs to differentiate into sweat gland cells for sweat gland regeneration through ectodysplasin (EDA) gene transfection.</p><p><b>METHODS</b>The dynamic expression of EDA and EDA receptor (EDAR) were firstly observed in the sweat gland formation during embryological development. After transfection with EDA expression vector, human BM-MSCs were transplanted into the injured areas of burn animal models. The regeneration of sweat glands was identified by perspiration test and immunohistochemical analysis.</p><p><b>RESULTS</b>Endogenous expression of EDA and EDAR correlated with sweat gland development in human fetal skin. After EDA transfection, BM-MSC acquired a sweat-gland-cell phenotype, evidenced by their expression of sweat gland markers by flow cytometry analysis. Immunohistochemical staining revealed a markedly contribution of EDA-transfected BM-MSCs to the regeneration of sweat glands in the scalded paws. Positive rate for perspiration test for the paws treated with EDA-transfected BM-MSCs was significantly higher than those treated with BM-MSCs or EDA expression vector (P < 0.05).</p><p><b>CONCLUSIONS</b>Our results confirmed the important role of EDA in the development of sweat gland. BM-MSCs transfected with EDA significantly improved the sweat-gland regeneration. This study suggests the potential application of EDA-modified MSCs for the repair and regeneration of injured skin and its appendages.</p>

Effect of mycophenolate mofetil on the expression of early inflammatory reaction in diabetic rats / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of mycophenolate mofetil(MMF) on early inflammatory reaction of renal lesion in streptozotocin(STZ)-induced diabetic rats.@*METHODS@#Thirty-six male Sprague-Dawley rats were randomly divided into 3 groups after uninephrectomy: normal control group, diabetic model group, and MMF-treated group. Six rats in each group were sacrificed at the 4th week and 14th week after STZ injection. Twenty-four hour urinary protein (24 h Upro) count was measured before death. The expressions of regulated on activation of normal T expressed and secreted (RANTES),ectodermal dysplasia (ED-1)and Col-IV protein in the renal tissue were detected by immunohistochemistry. The expression of RANTES mRNA in the renal tissue was detected by RT-PCR.@*RESULTS@#MMF prevented the increasing of 24h Upro in diabetic rats,and the expressions of RANTES,ED-1,Col-IV protein and RANTES mRNA in the kidney of MMF-treated rats were significantly decreased.@*CONCLUSION@#MMF plays an early renal protective role in diabetic nephropathy, possibly through inhibition of early inflammatory reaction.